Details of a Researcher - Matsumoto, Morio

Papers - Matsumoto, Morio

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Differentiation of spinal giant cell tumors from chordomas by using a scoring system

Tsuji Takashi, Chiba Kazuhiro, Watanabe Kota, Ishii Ken, Nakamura Masaya, Nishiwaki Yuji, Matsumoto Morio

European Journal of Orthopaedic Surgery and Traumatology 1 - 6 2016.07

ISSN 1633-8065

Introduction: Few reports have compared the clinical features and imaging characteristics of giant cell tumor and chordoma of the spine. The aim of the present study was to investigate whether the two types of tumors could be differentially diagnosed, by comparing clinical characteristics as well as magnetic resonance imaging (MRI) or computed tomography (CT) findings and then scoring the characteristic findings. Methods: A total of 18 patients were retrospectively assessed. To elucidate the characteristic findings, we investigated the following 10 items: age at diagnosis, sex, and site of occurrence; for MRI findings, the pattern of tumor expansion, T1-weighted images, T2-weighted images, septal structure, and cystic changes; and for CT findings, calcification or residual bone fragments and incomplete bone shells. Then, we developed a unique scoring system and investigated whether the two tumors could be differentiated by this scoring system. Results: Six items, including, age, site of occurrence, tumor expansion pattern, T2-weighted images, septal structure, and incomplete bone shells, were significantly different between giant cell tumor and chordoma patients. By using newly developed scoring system, the mean scores of 0.9 ± 0.6 (range 0–2) for giant cell tumor and 4.8 ± 1.5 (range 3–6) for chordoma patients were significantly different (P <0.001), thereby allowing the differential diagnosis by setting the cutoff value to three. Conclusions: We found that the six items were useful for differentially diagnosing giant cell tumor and chordoma. These results indicate that it may be possible to distinguish the two types of tumor by scoring these items.

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Adamantinoma of the distal femur diagnosed 5 years after initial surgery

Cao Kai, Susa Michiro, Watanabe Itsuo, Nishimoto Kazumasa, Horiuchi Keisuke, Sasaki Aya, Hayashi Yuichiro, Emoto Katsura, Kameyama Kaori, Nakamura Masaya, Matsumoto Morio, Morioka Hideo

Journal of Medical Case Reports 10 ( 1 ) 2016.06

ISSN 1752-1947

Background: Adamantinoma arising in the femur is extremely rare. We report a case of an adamantinoma occurring in the right medial femoral condyle that was diagnosed 5 years after the primary surgery. Case presentation: A 74-year-old Asian woman first complained of right knee pain without any cause. Radiographs demonstrated a 4×4.5 cm osteolytic lesion in her medial femoral condyle. Magnetic resonance imaging revealed a lesion which showed low signal on both T1 and T2-weighted image, and enhanced signal with gadolinium contrast administration. She underwent a wide resection of the lesion and was reconstructed with a tumor endoprosthesis. On histological examination, the tumor showed clusters of spindle-shaped and squamoid epithelial cells among the fibrous stroma. Adamantinoma was considered, however, the diagnosis was inconclusive due to the unusual localization and her age. Moreover, it was difficult to exclude metastatic carcinoma. Five years later, she was diagnosed with an abnormal shadow occupying the upper lobe of her right lung in a routine physical examination. She subsequently underwent a resection of the lung mass which histologically showed proliferation of spindle-shaped and squamoid epithelial cells. The histological similarity of the lung tumor and the femoral tumor led to the diagnosis of adamantinoma arising in her right medial femoral condyle with metastasis to the upper lobe of her right lung. Conclusion: In this case report, we report the clinical, radiographic, and histological features of an adamantinoma arising in the distal femur with a review of the literature.

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Smad2/3 proteins are required for immobilization-induced skeletal muscle atrophy

Tando Toshimi, Hirayama Akiyoshi, Furukawa Mitsuru, Sato Yuiko, Kobayashi Tami, Funayama Atsushi, Kanaji Arihiko, Hao Wu, Watanabe Ryuichi, Morita Mayu, Oike Takatsugu, Miyamoto Kana, Soga Tomoyoshi, Nomura Masatoshi, Yoshimura Akihiko, Tomita Masaru, Matsumoto Morio, Nakamura Masaya, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 291 ( 23 ) 12184 - 12194 2016.06

ISSN 0021-9258

Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.

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Geographic and ethnic variations in radiographic disability thresholds

Ames Christopher, Gammal Isaac, Matsumoto Morio, Hosogane Naobumi, Smith Justin S., Protopsaltis Themistocles, Yamato Yu, Matsuyama Yukihiro, Taneichi Hiroshi, Lafage Renaud, Ferrero Emmanuelle, Schwab Frank J., Lafage Virginie

Neurosurgery 78 ( 6 ) 793 - 800 2016.06

ISSN 0148-396X

BACKGROUND: Thresholds for spinal pelvic parameters in adult spinal deformity (ASD) were previously defined in North American patients and are commonly used to guide surgical planning. However, it is unclear whether these same threshold parameters can be more widely applied in other geographic regions and in other ethnicities. OBJECTIVE: To evaluate the variation in the radiographic disability thresholds between North American and Japanese ASD populations and to adjust sagittal modifier thresholds accordingly. METHODS: Retrospective case series of 717 patients with ASD who had baseline radiographs and Oswestry Disability Index (ODI) from North America (n 518) and Japan (n 199) were studied. Patients were compared at baseline for ODI, ODI offset from age- and ethnic-specific values (ODIni), and radiographic parameters. RESULTS: Significant differences in classification were observed: A greater proportion of Japanese patients had marked pelvic tilt deformity, whereas a greater proportion of US patients had marked SVA deformity; no difference in the pelvic incidence-lumbar lordosis mismatch sagittal modifier was observed. Health-related quality-of-life scores also differed, with a greater ODI raw value observed in the US patients but similar ODIni scores between cohorts. Stratifying ODIni scores by sagittal modifier grades revealed similar disability scores corresponding to the 0 to + thresholds for pelvic tilt, pelvic incidence-lumbar lordosis mismatch, and sagittal vertical axis across ethnicities. Finally, linear regression analysis demonstrated that compared with US patients, Japanese patients had a lower estimated ODI corresponding to established thresholds of radiographic deformity. CONCLUSION: Our findings demonstrate significant variability in health-related quality-of-life measures and radiographic parameters between North American and Japanese patients, supporting the need for population-adjusted sagittal modifiers to more accurately classify deformity.

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Pseudoarthrosis of the ilium after periacetabular osteotomy that was treated by cemented total hip arthroplasty

Kanaji Arihiko, Nishiwaki Toru, Oya Akihito, Maehara Kazuyuki, Maehara Hideki, Oishi Teruyo, Yamada Harumoto, Suda Yasunori, Nakamura Masaya, Matsumoto Morio

Journal of Medical Case Reports 10 ( 1 ) 2016.05

ISSN 1752-1947

Background: Preserving the hip joint to delay arthroplasty for patients with acetabular dysplasia-associated early-stage osteoarthritis has become more common, and several surgical procedures have demonstrated pain relief and improved hip joint function. Periacetabular osteotomy, one of the joint-preserving surgical procedures of the hip, provides favorable outcomes, although there are no reports of total hip arthroplasty being used to treat pseudoarthrosis of the periacetabular osteotomy segment. Therefore, we report a case of pseudoarthrosis in the osteotomy segment after periacetabular osteotomy. The patient was treated using modified total hip arthroplasty and achieved a favorable short-term outcome. Case presentation: A 62-year-old Japanese woman was diagnosed with bilateral acetabular dysplasia at the age of 50 years, and underwent right and left periacetabular osteotomy at the ages of 52 and 55 years, respectively. When she was 61-years old, she experienced repeated episodes of left coxalgia during walking, with increasing pain at rest, and subsequently visited our department. Plain radiography and computed tomography of her left hip joint confirmed pseudoarthrosis of the periacetabular osteotomy segment. In addition, narrowing of her left hip joint space was observed, which indicated advanced osteoarthritis of the hip. Therefore, she underwent left total hip arthroplasty when she was 62-years old. During the surgery, fibrous fusion of the periacetabular osteotomy segment was confirmed via fluoroscopy, although no abnormal mobility was observed. Thus, the osteotomy segment was fixed with one absorbable screw and two bone pegs (which were prepared using allogeneic bone), and the acetabular cup was fixed using cement. Her postoperative course was generally favorable and bone fusion of the periacetabular osteotomy segment was confirmed at 3 years and 6 months after surgery. Her modified Harris hip score was 43 before the surgery and had improved to 90 at the final follow-up. Conclusions: Modified total hip arthroplasty was successfully used to treat osteoarthritis of the hip and pseudoarthrosis of the periacetabular osteotomy segment. This procedure achieved pseudoarthrosis region bone fusion and a favorable postoperative outcome.

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Potential Involvement of Obesity-associated Chronic Inflammation in the Pathogenesis of Idiopathic Spinal Epidural Lipomatosis

Fujita Nobuyuki, Hosogane Naobumi, Hikata Tomohiro, Iwanami Akio, Watanabe Kota, Shiono Yuta, Okada Eijiro, Ishikawa Masayuki, Tsuji Takashi, Shimoda Masayuki, Horiuchi Keisuke, Nakamura Masaya, Matsumoto Morio, Ishii Ken

Spine 2016.04

ISSN 0362-2436

STUDY DESIGN.: Multicenter case–control study. OBJECTIVE.: To characterize the pathogenesis of idiopathic spinal epidural lipomatosis (SEL). SUMMARY OF BACKGROUND DATA.: SEL is often associated with the history of steroid use or endocrine disorders; however, the pathogenesis of idiopathic SEL remains poorly understood. METHODS.: Sixteen patients who underwent lumbar decompression surgery due to severe idiopathic SEL were included in the study (L group, 15 males and 1 female; mean age, 71.5 years). Fifteen patients without SEL, who underwent decompression surgery for lumbar canal stenosis, were selected as controls (C group, 14 males and 1 female; mean age, 70.3 years). The following parameters were analyzed in these two groups: body mass index (BMI), medical history, histology, the size of adipocytes in the epidural fat (EF) tissues, and the expression level of the transcripts for adiponectin, leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8. RESULTS.: The mean BMI of the L group was significantly higher than that of the C group (29.1 vs. 25.2?kg/m, P?=?0.006), and there was a significant correlation between BMI and the width of EF in both groups. The average adipocyte size in the EF was significantly larger in the L group than in the C group (2846.8 vs. 1699.0?μm, P?=?0.017). Furthermore, the expression levels of the transcripts for TNF-α and IL-1β in the L group were significantly higher than those in the C group [2.59-fold increase (P?=?0.023) and 2.60-fold increase (P?=?0.015), respectively]. CONCLUSION.: Our data suggest that the pathogenesis of idiopathic SEL is associated with obesity. In addition, the increased expression of two major inflammatory cytokines in the EF in the L group may indicate that SEL is causally related to chronic inflammation.Level of Evidence: 3

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Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts

Umeyama Kazuhiro, Watanabe Kota, Watanabe Masahito, Horiuchi Keisuke, Nakano Kazuaki, Kitashiro Masateru, Matsunari Hitomi, Kimura Tokuhiro, Arima Yoshimi, Sampetrean Oltea, Nagaya Masaki, Saito Masahiro, Saya Hideyuki, Kosaki Kenjiro, Nagashima Hiroshi, Matsumoto Morio

Scientific Reports 6 2016.04

Marfan syndrome (MFS) is an autosomal dominant genetic disease caused by abnormal formation of the extracellular matrix with an incidence of 1 in 3, 000 to 5, 000. Patients with Marfan syndrome experience poor quality of life caused by skeletal disorders such as scoliosis, and they are at high risk of sudden death from cardiovascular impairment. Suitable animal models of MFS are essential for conquering this intractable disease. In particular, studies employing pig models will likely provide valuable information that can be extrapolated to humans because of the physiological and anatomical similarities between the two species. Here we describe the generation of heterozygous fibrillin-1 (FBN1) mutant cloned pigs (+/Glu433AsnfsX98) using genome editing and somatic cell nuclear transfer technologies. The FBN1 mutant pigs exhibited phenotypes resembling those of humans with MFS, such as scoliosis, pectus excavatum, delayed mineralization of the epiphysis and disrupted structure of elastic fibres of the aortic medial tissue. These findings indicate the value of FBN1 mutant pigs as a model for understanding the pathogenesis of MFS and for developing treatments.

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A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection

Funao Haruki, Nagai Shigenori, Sasaki Aya, Hoshikawa Tomoyuki, Tsuji Takashi, Okada Yasunori, Koyasu Shigeo, Toyama Yoshiaki, Nakamura Masaya, Aizawa Mamoru, Matsumoto Morio, Ishii Ken

Scientific Reports 6 2016.03

Various silver-coated implants have been developed to prevent implant-associated infections, and have shown dramatic effects in vitro. However, the in vivo results have been inconsistent. Recent in vitro studies showed that silver exerts antibacterial activity by mediating the generation of reactive oxygen species in the presence of oxygen. To maintain its antibacterial activity in vivo, the silver should remain in an ionic state and be stably bound to the implant surface. Here, we developed a novel bacteria-resistant hydroxyapatite film in which ionic silver is immobilized via inositol hexaphosphate chelation using a low-heat immersion process. This bacteria-resistant coating demonstrated significant antibacterial activity both in vitro and in vivo. In a murine bioluminescent osteomyelitis model, no bacteria were detectable 21 days after inoculation with S. aureus and placement of this implant. Serum interleukin-6 was elevated in the acute phase in this model, but it was significantly lower in the ionic-silver group than the control group on day 2. Serum C-reactive protein remained significantly higher in the control group than the ionic-silver group on day 14. Because this coating is produced by a low-heat immersion process, it can be applied to complex structures of various materials, to provide significant protection against implant-associated infections.

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Subcutaneous flexor tendon rupture in patients with rheumatoid arthritis

Funahashi Takuya, Suzuki Taku, Iwamoto Takuji, Shizu Kanae, Matsumura Noboru, Ochi Kensuke, Ikari Katsunori, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki, Suzuki Katsuji, Yamada Harumoto

Modern Rheumatology 1 - 4 2016.03

ISSN 1439-7595

Objective: We examined the clinical features and functional outcomes of surgically repaired subcutaneous flexor tendon ruptures in patients with rheumatoid arthritis (RA). Methods: This retrospective study included 41 fingers of 24 RA patients who underwent surgical treatment for flexor tendon ruptures. Evaluations performed at the time of presentation following rupture were C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score in 28 joints (DAS28)-ESR, as well as Larsen grading for carpal bone destruction. The ruptured tendon and postoperative active range of motion (ROM) of digits were also examined. Results: The mean CRP was 2.4 mg/dl, ESR was 52 mm/h, and the DAS28-ESR was 4.5. Carpal bone destruction according to Larsen grade IV–V was observed in 18/24 patients. Affected digits were most commonly the thumb (12) and the ring and little fingers (9 each). Tendon ruptures were most common in the carpal tunnel in zone IV. The mean postoperative finger ROM (flexion/extension) was 38°/2° for the interphalangeal (IP) joint of the thumb and 23°/−2° for the distal interphalangeal joint of the other four fingers. Conclusions: Patients with flexor tendon ruptures present with high disease activity and advanced bone destruction. It is important to reduce the risk of progressive bone destruction and subsequent tendon rupture via tight control of disease activity.

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Comparison of surgical treatments for triple extensor tendon ruptures in rheumatoid hands

Suzuki Taku, Iwamoto Takuji, Ikegami Hiroyasu, Sakuma Yu, Ikari Katsunori, Matsumura Noboru, Ochi Kensuke, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki

Modern Rheumatology 26 ( 2 ) 206 - 210 2016.03

ISSN 1439-7595

Objective. This retrospective study was designed to evaluate the outcomes of four different surgical reconstructions for extensor tendon ruptures in ulnar three fingers in 48 patients with rheumatoid arthritis. Methods. The following four techniques were performed; palmaris longus tendon grafting (PL group; n = 9), extensor indicis proprius (EIP) tendon transfers (EIP group; n = 8), end-to-side transfers with tension-reduced early mobilization (End-to-side group; n = 16), and a combination of end-to-side and EIP transfers (Combination group; n = 15). Loss of extension was evaluated to determine the mean postoperative range of motion of the metacarpophalangeal (MP) joint and clinical outcomes were categorized using modified Geldmacher criteria. Results. Combination group demonstrated the best mean MP joint extension (- 3°), followed by End-to-side group (- 12°), EIP group (- 16°), and PL group (- 21°). Combination group yielded the best clinical outcomes with all cases showing good results. Conclusions. The combination of end-to-side and EIP transfer was an effective surgical reconstruction procedure for triple fingers extension loss.

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Hif1α is required for osteoclast activation and bone loss in male osteoporosis

Tando Toshimi, Sato Yuiko, Miyamoto Kana, Morita Mayu, Kobayashi Tami, Funayama Atsushi, Kanaji Arihiko, Hao Wu, Watanabe Ryuichi, Oike Takatsugu, Nakamura Masaya, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Biochemical and Biophysical Research Communications 470 ( 2 ) 391 - 396 2016.02

ISSN 0006-291X

The number of osteoporosis patients is increasing not only in women but in men. Male osteoporosis occurs due to aging or androgen depletion therapies, leading to fractures. However, molecular mechanisms underlying male osteoporosis remain unidentified. Here, we show that hypoxia inducible factor 1 alpha (Hif1α) is required for development of testosterone deficiency-induced male osteoporosis. We found that in mice Hif1α protein accumulates in osteoclasts following orchidectomy (ORX) in vivo. In vitro, Hif1α protein accumulated in osteoclasts cultured in hypoxic conditions, but Hif1α protein rather than mRNA levels were suppressed by testosterone treatment, even in hypoxia. Administration of a Hif1α inhibitor to ORX mice abrogated testosterone deficiency-induced osteoclast activation and bone loss but did not alter osteoclast activities or bone phenotypes in sham-operated, testosterone-sufficient animals. We conclude that Hif1α protein accumulation due to testosterone-deficiency promotes development of male osteoporosis. Thus Hif1α protein could be targeted to inhibit pathologically-activated osteoclasts under testosterone-deficient conditions to treat male osteoporosis patients.

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Reliability analysis of spino-pelvic parameters in adult spinal deformity

Chen Rui Qiang, Hosogane Naobumi, Watanabe Kota, Funao Haruki, Okada Eijiro, Fujita Nobuyuki, Hikata Tomohiro, Iwanami Akio, Tsuji Takashi, Ishii Ken, Abe Takayuki, Toyama Yoshiaki, Nakamura Masaya, Matsumoto Morio

Spine 41 ( 4 ) 320 - 327 2016.02

ISSN 0362-2436

Study Design. Retrospective study. Objective. To examine the reliabilities of sagittal spino-pelvic alignment measurements using whole spine-pelvic and local pelvic radiographs and to determine whether spinal deformity affects these reliabilities. Summary of Background Data. Sagittal spino-pelvic alignment is important in adult spinal deformity patients (ASD). Spino-pelvic parameters are closely related to health-related quality of life and indispensable for surgical planning. However, few studies have focused on the reliability of these measurements. Methods. Three spino-pelvic parameters, pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in 2 patient groups: 33 adult scoliosis (AS) and 33 nondeformity (ND) patients, using whole spine-pelvic lateral radiographs (whole spine radiographs) and local pelvic lateral radiographs (local pelvic radiographs), by 5 experienced spine surgeons. Intra- and interobserver reliabilities for each procedure were evaluated by intraclass correlation coefficients (ICC). The interobserver reliability differences between the 2 procedures were statistically evaluated. The difference between the largest and smallest measurements among the 5 observers was also evaluated in the AS and ND groups. Results. Measurement of the 3 parameters using whole spine or local pelvic radiographs showed good to excellent intraobserver reliability (range of ICC: 0.820-0.935). The interobserver reliabilities of PI and PT from local pelvic radiographs were significantly higher than those from whole spine radiographs (P

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Calculation of the target lumbar lordosis angle for restoring an optimal pelvic tilt in elderly patients with adult spinal deformity

Yamato Yu, Hasegawa Tomohiko, Kobayashi Sho, Yasuda Tatsuya, Togawa Daisuke, Arima Hideyuki, Oe Shin, Iida Takahiro, Matsumura Akira, Hosogane Naobumi, Matsumoto Morio, Matsuyama Yukihiro

Spine 41 ( 4 ) E211 - E217 2016.02

ISSN 0362-2436

Study Design. This investigation consisted of a cross-sectional study and a retrospective multicenter case series. Objective. This investigation sought to identify the ideal lumbar lordosis (LL) angle for restoring an optimal pelvic tilt (PT) in patients with adult spinal deformity (ASD). Summary of Background Data. To achieve successful corrective fusion in ASD patients with sagittal imbalance, it is essential to correct the sagittal spinal alignment and obtain a suitable pelvic inclination. We determined the LL angle that would restore the optimal PT following ASD surgery. Methods. The cross-sectional study included 184 elderly volunteers (mean age 64 years) with an Oswestry Disability Index score less than 20%. The relationship between PT or LL and the pelvic incidence (PI) in normal individuals was investigated. The second study included 116 ASD patients (mean age 66 years) who underwent thoracolumbar corrective fusion at 1 of 4 spine centers. The postoperative PT values were calculated using the parameters measured. On the basis of these studies, an ideal LL angle was determined. Results. In the cross-sectional study, the linear regression equation for the optimal PT as a function of PI was "optimal PT=0.47×PI-7.5." In the second study, the postoperative PT was determined as a function of PI and corrected LL, using the equation "postoperative PT=0.7×PI-0.5×corrected LL+8.1." The target LL angle was determined by mathematically equalizing the PTs of these 2 equations: "target LL=0.45×PI+31.8." Conclusion. The ideal LL angle can be determined using the equation "LL=0.45×PI+31.8," which can be used as a reference during surgical planning in ASD cases.

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Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

Kawabata Soya, Takano Morito, Numasawa-Kuroiwa Yuko, Itakura Go, Kobayashi Yoshiomi, Nishiyama Yuichiro, Sugai Keiko, Nishimura Soraya, Iwai Hiroki, Isoda Miho, Shibata Shinsuke, Kohyama Jun, Iwanami Akio, Toyama Yoshiaki, Matsumoto Morio, Nakamura Masaya, Okano Hideyuki

Stem Cell Reports 6 ( 1 ) 1 - 8 2016.01

ISSN 2213-6711

Murine- and human-induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NS/PCs) promote functional recovery following transplantation into the injured spinal cord in rodents and primates. Although remyelination of spared demyelinated axons is a critical mechanism in the regeneration of the injured spinal cord, human iPSC-NS/PCs predominantly differentiate into neurons both in vitro and in vivo. We therefore took advantage of our recently developed protocol to obtain human-induced pluripotent stem cell-derived oligodendrocyte precursor cell-enriched neural stem/progenitor cells and report the benefits of transplanting these cells in a spinal cord injury (SCI) model. We describe how this approach contributes to the robust remyelination of demyelinated axons and facilitates functional recovery after SCI.

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Vitamin D deficiency with high intact PTH levels is more common in younger than in older women

Miyamoto Takeshi, Katsuyama Eri, Kanagawa Hiroya, Fujie Atsuhiro, Miyamoto Hiroya, Yoshida Shigeyuki, Mori Tomoaki, Miyamoto Kana, Sato Yuiko, Kobayashi Tami, Nakamura Masaya, Matsumoto Morio, Nishiwaki Yuji, Hirose Hiroshi, Kanda Takeshi, Saito Ikuo, Toyama Yoshiaki

Keio Journal of Medicine 65 ( 2 ) 33 - 38 2016

ISSN 0022-9717

Low serum 25-hydroxyvitamin D (25(OH)D) levels are implicated as a risk factor for hip and spine fractures. Studies of the relation between 25(OH)D levels and fractures have primarily involved elderly osteoporosis patients or patients with fractures; however, the serum 25(OH)D and parathyroid hormone (PTH) status in younger adult populations remains largely unknown. We evaluated serum 25(OH)D and intact PTH levels in 411 women aged 39–64 years who were not receiving medication for osteoporosis or other bone diseases. Serum 25(OH)D levels were positively correlated with age (P = 0.019), whereas intact PTH levels were inversely correlated with 25(OH)D levels (P <0.001). Thus, low vitamin D levels with high intact PTH levels were more common in younger than in older women. Our data show that serum 25(OH)D insufficiency could be a more serious concern in the younger population than had been previously anticipated. Because serum 25(OH)D insufficiency is reportedly a risk factor for hip and spine fracture, the number of fracture patients could increase in the future, suggesting that we may need to correct the serum vitamin D/intact PTH status to prevent future osteoporosis.

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Generation and characterization of a novel shoulder contracture mouse model

Oki Satoshi, Shirasawa Hideyuki, Yoda Masaki, Matsumura Noboru, Tohmonda Takahide, Yuasa Kazuki, Nakamura Masaya, Matsumoto Morio, Horiuchi Keisuke

Journal of Orthopaedic Research 33 ( 11 ) 1732 - 1738 2015.11

ISSN 0736-0266

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self-limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes.

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A Novel Percutaneous Guide Wire (S-Wire) for Percutaneous Pedicle Screw Insertion

Ishii Ken, Kaneko Yasuhito, Funao Haruki, Ishihara Shinichi, Shinohara Akira, Nakanishi Kazuo, Hikata Tomohiro, Fujita Nobuyuki, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nagura Takeo, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

Surgical Innovation 22 ( 5 ) 469 - 473 2015.10

ISSN 1553-3506

Purpose. Minimally invasive spine stabilization (MISt) procedures, including MIS-transforaminal lumbar interbody fusion (MIS-TLIF), rely on precise placement of percutaneous pedicle screws (PPS). Serious intraoperative complications associated with PPS placement include great vessel and bowel injuries due to the guide-wire's anterior migration and penetration through the anterior aspect of the vertebral body. To address this issue, we developed a novel percutaneous guide wire (S-wire) and compared the biomechanical characteristics of S-wire and conventional wire in cadaveric spines, and to evaluate the S-wire's efficacy and safety in a clinical trial. Methods. The S-wire is hollow, with braided wires extending at one tip. We compared the push-out and penetration forces of the S-wire and conventional wire in fresh cadaveric lumbar spines, from L1 to L5. Results. Push-out forces caused the braided tip of the S-wire to bend or spread, and thus to resist anterior migration. The mean push-out forces for the S-wire and conventional wire were 15.5 ± 1.9 and 5.7 ± 0.8 N, respectively (P <.0001); the mean penetration forces were 69.1 ± 4.2 and 37.1± 4.8 N, respectively (P <.0005). There was no wire breakage or anterior-wall penetration in a clinical trial of 922 S-wires; interestingly, the pull-out force increased in 780 (84.6%) S-wires after placement. Conclusions. The mean push-out and penetration forces for the S-wire were approximately 3 and 2 times greater than those of conventional wire, respectively. The S-wire effectively prevented guide-wire anterior migration and penetration of the anterior vertebral-body wall. The S-wire device should effectively improve the safety of MISt procedures, including MIS-TLIF and percutaneous kyphoplasty in selected patient with osteoporosis.

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Effects of femoral bone tunnel characteristics on graft-bending angle in double-bundle anterior cruciate ligament reconstruction

Niki Yasuo, Nagai Katsuya, Harato Kengo, Suda Yasunori, Nakamura Masaya, Matsumoto Morio

Knee Surgery, Sports Traumatology, Arthroscopy 2015.08

ISSN 0942-2056

Purpose: Bone tunnel creation techniques influence the 3-dimensional (3D) position of bone tunnels and graft-bending angle in anterior cruciate ligament (ACL) reconstruction. This study assessed graft-bending angle and 3D characteristics of femoral bone tunnels and compared them between outside-in (OI) and transportal (TP) techniques. Methods: Participants comprised 64 patients who underwent anatomic double-bundle ACL reconstruction, allocated to OI and TP groups (n = 32 each). The graft orientation plane exhibiting the largest graft-bending angle at the femoral tunnel aperture with the knee in extension was reconstructed from CT data using 3D imaging software. In this plane, graft-bending angle was compared between the OI and TP techniques. Results: Although positionings of the intra-articular apertures of the femoral and tibial bone tunnels were similar, several spatial parameters of bone tunnels differed between techniques. Graft-bending angles of both anteromedial and posterolateral bundles were significantly more acute with the OI technique than with the TP technique. On coronal-plane CT, angle of the bone tunnel axis relative to the distal condylar axis correlated negatively with graft-bending angle, while in the axial plane, angle of the bone tunnel axis relative to the posterior condylar axis correlated positively with graft-bending angle. Lysholm score, pivot shift test, and anteroposterior laxity at >2.5-year follow-up demonstrated no significant differences between techniques. Discussion: Different bone tunnel directions in OI and TP techniques substantially affected graft-bending angle, despite similar positionings of the intra-articular apertures. Graft-bending angle with the OI technique was acute, but risk of posterior blowout of the lateral femoral condyle was decreased. Surgeons should create the femoral tunnel while considering an obtuse graft-bending angle without increasing the risk of posterior blowout. Level of evidence: III.

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Comparison of surgical treatments for triple extensor tendon ruptures in rheumatoid hands

Suzuki Taku, Iwamoto Takuji, Ikegami Hiroyasu, Sakuma Y., Ikari Katsunori, Matsumura Noboru, Ochi Kensuke, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki

Modern Rheumatology 2015.08

ISSN 1439-7595

Objective. This retrospective study was designed to evaluate the outcomes of four different surgical reconstructions for extensor tendon ruptures in ulnar three fingers in 48 patients with rheumatoid arthritis. Methods. The following four techniques were performed; palmaris longus tendon grafting (PL group; n = 9), extensor indicis proprius (EIP) tendon transfers (EIP group; n = 8), end-to-side transfers with tension-reduced early mobilization (End-to-side group; n = 16), and a combination of end-to-side and EIP transfers (Combination group; n = 15). Loss of extension was evaluated to determine the mean postoperative range of motion of the metacarpophalangeal (MP) joint and clinical outcomes were categorized using modified Geldmacher criteria. Results. Combination group demonstrated the best mean MP joint extension (− 3°), followed by End-to-side group (− 12°), EIP group (− 16°), and PL group (− 21°). Combination group yielded the best clinical outcomes with all cases showing good results. Conclusions. The combination of end-to-side and EIP transfer was an effective surgical reconstruction procedure for triple fingers extension loss.

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IRE1α/XBP1-mediated branch of the unfolded protein response regulates osteoclastogenesis

Tohmonda Takahide, Yoda Masaki, Iwawaki Takao, Matsumoto Morio, Nakamura Masaya, Mikoshiba Katsuhiko, Toyama Yoshiaki, Horiuchi Keisuke

Journal of Clinical Investigation 125 ( 8 ) 3269 - 3279 2015.08

ISSN 0021-9738

The unfolded protein response (UPR) is a cellular adaptive mechanism that is activated in response to the accumulation of unfolded proteins in the endoplasmic reticulum. The inositol-requiring protein-1α/X-box-binding protein-mediated (IRE1α/ XBP1-mediated) branch of the UPR is highly conserved and has also been shown to regulate various cell-fate decisions. Herein, we have demonstrated a crucial role for the IREα/XBP1-mediated arm of the UPR in osteoclast differentiation. Using murine models, we found that the conditional abrogation of IRE1α in bone marrow cells increases bone mass as the result of defective osteoclastic bone resorption. In osteoclast precursors, IRE1α was transiently activated during osteoclastogenesis, and suppression of the IRE1α/XBP1 pathway in these cells substantially inhibited the formation of multinucleated osteoclasts in vitro. We determined that XBP1 directly binds the promoter and induces transcription of the gene encoding the master regulator of osteoclastogenesis nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Moreover, activation of IRE1α was partially dependent on Ca2+ oscillation mediated by inositol 1,4,5-trisphosphate receptors 2 and 3 (ITPR2 and ITPR3) in the endoplasmic reticulum, as pharmacological inhibition or deletion of these receptors markedly decreased Xbp1 mRNA processing. The present study thus reveals an intracellular pathway that integrates the UPR and osteoclast differentiation through activation of the IRE1α/XBP1 pathway.

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