研究

骨軟骨や腱、腫瘍、脊椎に関する臨床研究ならびに基礎研究を進めており、
変形性関節症の病態解明や筋骨格系の新治療開発に向けた研究を精力的に行っております。

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  2. 研究

研究

骨軟骨や腱、腫瘍、脊椎に関する臨床研究ならびに基礎研究を進めており、
変形性関節症の病態解明や筋骨格系の新治療開発に向けた研究を精力的に行っております。

骨・軟骨

骨形成におけるミトコンドリア機能の解析

細胞はミトコンドリアと解糖系によりATP生合成を行っています。当研究室ではこのATP生合成と骨格形成について解析を行っています。我々は、ミトコンドリア転写因子であるTfamを肢芽特異的に欠損したマウスを作成したところ、著名な四肢骨格変形を認め、多発骨折を発症しました。（下図）この解析により、ミトコンドリアにおける好気性ATP合成が骨格の正常な形成・維持及び生後の骨軟骨疾患に極めて重要な役割を果たしていることが示されました。

変形性膝関節症の病態解明および再生医療を含むその治療薬の開発

変形性膝関節症は世界中でも多い炎症性関節疾患で, 国内でもその罹患者は250,000人に上るとされています. 変形性膝関節症では軟骨変性・半月板損傷・滑膜炎・軟骨下骨変化など同時に引き起こされ, これらの病態が徐々に進行し患者の日常生活動作を障害します. その原因は環境・遺伝・関節力学・外傷・炎症性疾患・加齢など多岐に亘るため, 同疾患においてどのように軟骨代謝が制御されているかは十分明らかにされていません. そのため, 関節軟骨を回復したりその減少を止めるような変形性膝関節症の病態そのものを治療する変形性関節症病態修飾性治療薬(Disease modifying osteoarthritis drugs; DMOADs)は未だ開発されていません. 我々は, 変形性膝関節用の分子病態を解明し、低分子化合物によるDMOADsおよび軟骨再生治療の開発を目指しています。

運動刺激によるルブリシン(Prg4)発現メカニズムの解明
運動刺激によるルブリシン(Prg4)発現メカニズムの解明
(Ogawa H, et al. Genes Dev. 2014 15;28(2):127-39)
コルヒチンはPLC gamma1のリン酸をによるMMP13の発現を阻害することで軟骨変性を抑制する
コルヒチンはPLC gamma1のリン酸をによるMMP13の発現を阻害することで軟骨変性を抑制する.
(Takeuchi K, Ogawa H, et al. Osteoarthritis Cartilage. 2021 Nov;29(11):1564-1574)

脊椎

低分子ヘパリンを用いた骨再生研究

人口の高齢化に伴い、脊椎固定術・骨欠損部再建・偽関節治療・人工関節置換術など骨移植や早期骨癒合を必要とする状況は増加の一途を辿っています。その際、自家骨・他家骨・人工骨などが用いられますが、高い骨誘導能を有する生理活性物質と併用することで治療促進効果が期待されています。実際、海外では骨形成蛋白（bone morphogenic protein:BMP）が認可され、脊椎領域でも臨床応用されています。しかしながら、その生理活性物質を骨へ届けるdrug delivery system(DDS)が既存のものでは薬剤徐放が早いために高価なBMP が高用量必要となり、また局所の炎症反応による創部治癒遅延や骨吸収、異所性骨化を生じることが問題点の一つとなっています。そこで我々は、それらの問題を改善するべく低分子ヘパリンを用いた新規のDDSを開発し、臨床応用に向けて研究しています。

ラットにおける脊椎固定モデル（マイクロCT画像）

BMP-2を新規薬剤と併用することで、骨形成が促進しています。

コントロール
コントロール
BMP-2のみ
BMP-2のみ
新規薬剤とBMP-2併用
新規薬剤とBMP-2併用

腫瘍

骨肉腫は主に小児に発生する悪性骨腫瘍であり、国内で年間200例程度の発生しかない希少がんの一つです。現在の標準治療は術前後の化学療法と手術療法であり、これにより1970年代には10％前後であった5年生存率が現在では70％前後と大きく改善しました。しかし、ここ30年における治療成績の改善は得られていません。この原因の一つに化学療法に用いる薬剤への抵抗性があり、従来の抗がん剤とは異なるアプローチの治療法の開発が望まれています。 新しい腫瘍に対する治療アプローチの標的として、腫瘍細胞のエネルギー代謝があり、白血病や脳腫瘍、乳がんなどさまざな腫瘍においてエネルギー代謝を阻害することによる腫瘍の抑制効果が報告されています。そこで、骨肉腫においても細胞内のエネルギー代謝阻害が有用な新規治療となりうるのではないかと考え、我々の研究グループでは、骨肉腫細胞内のエネルギー代謝を抑制することによる抗腫瘍効果を明らかにし、新規治療の開発を目指して基礎研究を行なっています。 また、Ewing肉腫や明細胞肉腫などの骨軟部腫瘍は、染色体相互転座により様々な融合遺伝子を発現し、腫瘍発生に深く関与していることが明らかとなってきており、我々はこれまでにEWS/Fli-1融合遺伝子が血管内皮細胞増殖因子(VEGF)を調節していることやオーロラキナーゼ、サイクリン依存キナーゼを抑制することでEwing肉腫の細胞増殖が抑制できることなどを報告してきました。また、融合遺伝子EWS/ATF1の発現を誘導したトランスジェニックマウスから軟部腫瘍を発生させることに成功し、さらに明細胞肉腫の起源が神経堤由来の細胞であることを証明しました。このように骨肉腫以外の骨軟部腫瘍についても病態、分子メカニズムを解明し、その特性を利用した分子標的治療の開発を目指し研究を行なっています。

腱

腱は再生能力が低いため、腱が断裂してしまった場合、正常な腱の状態へと再生することは困難です。腱再生を促す治療の研究として幹細胞治療や成長因子治療、生体材料治療などが報告されていますが、いまだに実用できる治療薬はありません。当グループではこれまでにiPS細胞から腱細胞の分化誘導法を開発し、その分化誘導した腱細胞を損傷した腱へ細胞移植することで、腱再生が促され歩行機能が改善することを証明しました(図1)(Komura. Sci Rep. 2020)。また、成人と子供の腱断裂の手術成績を比較すると子供の腱断裂の方が良好な経過となりますが、マウスにおいても同様で、若齢のマウスでは腱切断後の腱の再生が良好です(図2)。若齢のマウスの遺伝子の働きを調べることで、若齢マウスでは、あるシグナルの遺伝子の発現が高いことを特定しました。このシグナルに着目し、高齢のマウスでこのシグナルを活性化することで腱の再生が促されることが分かりました。今後はこのシグナルを操作することで、腱断裂の治療につながるような新規治療薬の開発を目指しています。

図1

細胞移植なし
細胞移植なし
細胞移植あり
細胞移植あり

図2

若年マウス（7日齢）
若年マウス（7日齢）
高齢マウス（4ヵ月齢）
高齢マウス（4ヵ月齢）

業績

過去5年の業績

  1. Hirakawa A, Komura S, Akiyama H. Comments on "Flexor Tendon Rupture Due to Previously Undiagnosed Kienböck Disease: A Case Report".Hand (N Y). 2019 Jan;14(1):135-136. doi: 10.1177/1558944718795511.
  2. Iwata N, Komura S, Hirakawa A, Kanamori S, Masuda T, Ito Y, Akiyama H. Dorsal buttress plate fixation for the treatment of fracture-dislocation of the fifth carpometacarpal joint with avulsion fracture of the hamate: a case report. Arch Orthop Trauma Surg. 2019 Jan;139(1):135-139. doi: 10.1007/s00402-018-3072-0.
  3. Ogawa H, Matsumoto K, Akiyama H. ACL degeneration after an excessive increase in the medial proximal tibial angle with medial open wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2019 Jan 17. doi: 10.1007/s00167-019-05354-0.
  4. Hiramatsu Y, Fukuda A, Ogawa S, Goto N, Ikuta K, Tsuda M, Matsumoto Y, Kimura Y, Yoshioka T, Takada Y, Maruno T, Hanyu Y, Tsuruyama T, Wang Z, Akiyama H, Takaishi S, Miyoshi H, Taketo MM, Chiba T, Seno H. Arid1a is essential for intestinal stem cells through Sox9 regulation. Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1704-1713. doi: 10.1073/pnas.1804858116.
  5. Kawashima K, Shinozaki M, Tsugita M, Ishimaru OSD, Akiyama H. Modified Extension Block Technique for Bony Mallet Injury of the Hallux. J Foot Ankle Surg. 2019 May;58(3):596-598. doi: 10.1053/j.jfas.2018.09.018.
  6. Komura S, Hirakawa A, Ishizuka K, Matsushita Y, Akiyama H. Mini hook plate fixation for thumb ulnar collateral ligament avulsion fracture: A technical report. Orthop Traumatol Surg Res. 2019 May;105(3):429-433. doi: 10.1016/j.otsr.2019.01.008.
  7. Ono R, Komura S, Hirakawa A, Hirose H, Tsugita M, Masuda T, Ito Y, Akiyama H. Staged arthrodesis using the Masquelet technique for osteomyelitis of the finger with articular destruction: a report of two cases. Arch Orthop Trauma Surg. 2019 May 15. doi: 10.1007/s00402-019-03197-5. [Epub ahead of print]
  8. Komura S, Hirakawa A, Yamamoto K, Kato K, Nohara M, Matsushita Y, Masuda T, Akiyama H. Delayed rupture of the flexor tendons as a complication of malunited distal radius fracture after nonoperative management: A report of two cases. Trauma Case Rep. 2019 Apr 28;21:100198. doi: 10.1016/j.tcr.2019.100198. eCollection 2019 Jun.
  9. Tateuchi H, Akiyama H, Goto K, So K, Kuroda Y, Ichihashi N. Gait- and posture-related factors associated with changes in hip pain and physical function in patients with secondary hip osteoarthritis: a prospective cohort study. Arch Phys Med Rehabil. 2019 May 1. pii: S0003-9993(19)30293-X. doi: 10.1016/j.apmr.2019.04.006. [Epub ahead of print]
  10. Ogawa H, Matsumoto K, Akiyama H. Effect of increased posterior tibial slope on the anterior cruciate ligament status in medial open wedge high tibial osteotomy in an uninjured ACL population. Orthop Traumatol Surg Res. 2019 Jun 8. pii: S1877-0568(19)30164-1. doi: 10.1016/j.otsr.2019.05.003.
  11. Nagano A, Matsumoto S, Kawai A, Okuma T, Hiraga H, Matsumoto Y, Nishida Y, Yonemoto T, Hosaka M, Takahashi M, Yoshikawa H, Kunisada T, Asanuma K, Naka N, Emori M, Kubo T, Kawashima H, Kawamoto T, Yokoyama R, Tsukushi S, Sato K, Okamoto T, Hiraoka K, Morioka H, Tanaka K, Takagi T, Iwamoto Y, Ozaki T. J Orthop Sci. 2020 Mar;25(2):319-323. doi: 10.1016/j.jos.2019.04.008. Epub 2019 May 30. PMID: 31155441
  12. Hirose H, Ogawa H, Matsumoto K, Akiyama H. Periarticular injection of tranexamic acid promotes early recovery of the range of knee motion after total knee arthroplasty. J Orthop Surg (Hong Kong). 2019 Sep-Dec;27(3):2309499019864693. doi: 10.1177/2309499019864693.
  13. Komura S, Hirakawa A, Ishizuka K, Matsushita Y, Akiyama H. Response to the Letter by Feipeng Gong, Zhiqiang Fan, Xiaozheng Tang, Baofu Yu. Orthop Traumatol Surg Res. 2019 Aug 29. pii: S1877-0568(19)30198-7. doi: 10.1016/j.otsr.2019.07.001.
  14. Komura S, Ito K, Ohta S, Ukai T, Kabata M, Itakura F, Semi K, Matsuda Y, Hashimoto K, Shibata H, Sone M, Jo N, Sekiguchi K, Ohno T, Akiyama H, Shimizu K, Woltjen K, Ozawa M, Toguchida J, Yamamoto T, Yamada Y. Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas. Nat Commun. 2019 Sep 5;10(1):3999. doi: 10.1038/s41467-019-11745-1.
  15. Nozawa S, Fushimi K, Iwai C, Ishizuka K, Akiyama H. Repetitive distortion of the spinal cord owing to a pulsating arachnoid cyst: case illustration. J Neurosurg Spine. 2019 Sep 27:1-2. doi: 10.3171/2019.7.SPINE19660.
  16. Kuroda Y, Tanaka T, Miyagawa T, Kawai T, Goto K, Tanaka S, Matsuda S, Akiyama H. Classification of osteonecrosis of the femoral head: Who should have surgery? Bone Joint Res. 2019 Nov 2;8(10):451-458. doi: 10.1302/2046-3758.810.BJR-2019-0022.R1. eCollection 2019 Oct.
  17. Ogawa H, Matsumoto K, Sengoku M, Yoshioka H, Akiyama H. Arthroscopic repair of horizontal cleavage meniscus tears provides good clinical outcomes in spite of poor meniscus healing. Knee Surg Sports Traumatol Arthrosc. 2019 Nov 20. doi: 10.1007/s00167-019-05782-y. [Epub ahead of print]
  18. Ogawa H, Matsumoto K, Yoshioka H, Sengoku M, Akiyama H. Distal tibial tubercle osteotomy is superior to the proximal one for progression of patellofemoral osteoarthritis in medial opening wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2019 Dec 24. doi: 10.1007/s00167-019-05836-1. [Epub ahead of print]
  19. Matsumoto K, Ishimaru D, Ogawa H, Akiyama H. Joint Space Width, but Not Osteophyte Thickness, Is a Reliable Indicator of Degeneration of Lateral Knee Joint Cartilage. Acta Orthop Belg. 2019 Dec;85(4):494-501.
  20. Kawashima K, Terabayashi N, Asano H, Akiyama H. Classification of stress fractures of the first rib in adolescent athletes. J Pediatr Orthop B. 2020 Feb 8. doi: 10.1097/BPB.0000000000000720. [Epub ahead of print]
  21. Komura S, Hirakawa A, Masuda T, Nohara M, Kimura A, Matsushita Y, Akiyama H. Chronological changes in surgical outcomes after trapeziectomy with ligament reconstruction and tendon interposition arthroplasty for thumb carpometacarpal osteoarthritis. Orthop Traumatol Surg Res. 2020 Jan 22. pii: S1877-0568(20)30003-7. doi: 10.1016/j.otsr.2019.11.020. [Epub ahead of print]
  22. Matsumoto K, Ogawa H, Yoshioka H, Akiyama H. Differences in patient-reported outcomes between medial opening-wedge high tibial osteotomy and total knee arthroplasty. J Orthop Surg (Hong Kong). 2020 Jan-Apr;28(1):2309499019895636. doi: 10.1177/2309499019895636.
  23. Komura S, Satake T, Goto A, Aoki H, Shibata H, Ito K, Hirakawa A, Yamada Y, Akiyama H. Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice. Sci Rep. 2020 Mar 4;10(1):3992.
  24. Nagano A, Matsumoto S, Kawai A, Okuma T, Hiraga H, Matsumoto Y, Nishida Y, Yonemoto T, Hosaka M, Takahashi M, Yoshikawa H, Kunisada T, Asanuma K, Naka N, Emori M, Kubo T, Kawashima H, Kawamoto T, Yokoyama R, Tsukushi S, Sato K, Okamoto T, Hiraoka K, Morioka H, Tanaka K, Takagi T, Iwamoto Y, Ozaki T. Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients. J Orthop Sci. 2020 Mar;25(2):319-323. doi: 10.1016/j.jos.2019.04.008. Epub 2019 May 30.
  25. Matsumoto K, Ogawa H, Akiyama H. Radiographic characteristics of the hip joint in skeletally mature patients with multiple hereditary exostoses. Skeletal Radiol. 2020 May 30. doi: 10.1007/s00256-020-03482-0. Online ahead of print.
  26. Ogawa H, Matsumoto K, Akiyama H. Effects of lateral opening wedge and medial closing wedge distal femoral osteotomies on axial load stability. Knee. 2020 Jun;27(3):760-766. doi: 10.1016/j.knee.2020.04.019. Epub 2020 May 27.
  27. Ichikawa K, Ogawa H, Matsumoto K, Akiyama H. Double level derotation knee osteotomy for habitual patellar dislocation with femorotibial osteoarthritis in an adult. J Orthop Sci. 2020 Jun 17:S0949-2658(20)30132-9. doi: 10.1016/j.jos.2020.04.012. Online ahead of print.
  28. Matsumoto K, Ogawa H, Nozawa S, Akiyama H. An analysis of osteoporosis in patients with hereditary multiple exostoses. Osteoporos Int. 2020 Jul 8. doi: 10.1007/s00198-020-05533-7. Online ahead of print.
  29. Matsumoto K, Ishimaru D, Ogawa H, Komura S, Shimizu K, Akiyama H. Correlation between mutated genes and forearm deformity in patients with multiple osteochondroma. J Orthop Sci. 2020 Jul 4:S0949-2658(20)30151-2. doi: 10.1016/j.jos.2020.05.012. Online ahead of print.
  30. Iwai C, Fushimi K, Nozawa S, Mitsuishi N, Ogawa H, Maeda M, Kuramitsu N, Akiyama H. Spontaneous morphological remodelling of the O-C1 joint after posterior fusion for occipitocervical dislocation. Int J Neurosci. 2020 Sep 11:1-6. doi: 10.1080/00207454.2020.1818740. Online ahead of print.
  31. Kawashima K, Ogawa H, Komura S, Ishihara T, Yamaguchi Y, Akiyama H, Matsumoto K. Heparan sulfate deficiency leads to hypertrophic chondrocytes by increasing bone morphogenetic protein signaling. Osteoarthritis Cartilage. 2020 Aug 18:S1063-4584(20)31110-9. doi: 10.1016/j.joca.2020.08.003. Online ahead of print.
  32. Hirose H, Komura S, Hirakawa A, Okuda R, Kato K, Kanamori S, Masuda T, Ito Y, Akiyama H. Reverse radiodorsal artery-pedicled thumb metacarpal vascularized bone graft for osteochondral fracture of the thumb interphalangeal joint with a bone defect: A case report. Microsurgery. 2020 Oct 4. doi: 10.1002/micr.30663. Online ahead of print.
  33. Sugiyama T, Fushimi K, Nagano A, Tsugita M, Nozawa S, Iwai C, Akiyama H. The malignant transformation of osteoid osteoma in the cervical spine to high-grade osteosarcoma: a case report and review of literature. Br J Neurosurg. 2020 Nov 3:1-5. doi: 10.1080/02688697.2020.1842326. Online ahead of print.
  34. The malignant transformation of osteoid osteoma in the cervical spine to high-grade osteosarcoma: a case report and review of literature. Sugiyama T, Fushimi K, Nagano A, Tsugita M, Nozawa S, Iwai C, Akiyama H. Br J Neurosurg. 2023 Oct;37(5):1023-1027. doi: 10.1080/02688697.2020.1842326. Epub 2020 Nov 3. PMID: 33140986
  35. Ogawa H, Matsumoto K, Yoshioka H, Sengoku M, Akiyama H. Fracture of the tibial tubercle does not affect clinical outcomes in medial opening wedge high tibial osteotomy with distal tibial tubercle osteotomy. Arch Orthop Trauma Surg. 2020 Nov 23. doi: 10.1007/s00402-020-03688-w. Online ahead of print.PMID: 33226460
  36. Ogawa H, Matsumoto K, Sengoku M, Yoshioka H, Yamamoto K, Shimokawa T, Ohnishi K, Akiyama H. Clinical course and outcomes of simultaneous-versus staged-bilateral medial opening wedge high tibial osteotomy. Asia Pac J Sports Med Arthrosc Rehabil Technol. 2020 Dec 7;23:13-17. doi: 10.1016/j.asmart.2020.11.003. eCollection 2021 Jan.
  37. Komura S, Matsumoto K, Hirakawa A, Akiyama H. Natural History and Characteristics of Hand Exostoses in Multiple Hereditary Exostoses. J Hand Surg Am. 2021 Feb 25:S0363-5023(21)00001-0. doi: 10.1016/j.jhsa.2020.12.011.
  38. Ogawa H, Matsumoto K, Akiyama H. Functional assessment of the anterior cruciate ligament in knee osteoarthritis. Ogawa H, Matsumoto K, Akiyama H.J Orthop. 2020 Dec 29;23:175-179. doi: 10.1016/j.jor.2020.12.035. eCollection 2021 Jan-Feb.PMID: 33551609
  39. Deguchi H, Komura S, Hirakawa A, Satake T, Sohmiya K, Hirose H, Masuda T, Ito Y, Akiyama H. Radioscapholunate arthrodesis using a dorsal locking plate for neglected un-united distal radius fractures; a report of two cases. J Orthop Sci. 2021 Jan 4:S0949-2658(20)30363-8. doi: 10.1016/j.jos.2020.11.021.
  40. Komura S, Hirakawa A, Masuda T, Nohara M, Kimura A, Matsushita Y, Akiyama H. Does trapeziectomy with ligament reconstruction and tendon interposition arthroplasty correct the metacarpophalangeal joint hyperextension associated with trapeziometacarpal osteoarthritis? Arch Orthop Trauma Surg. 2021 Mar 1. doi: 10.1007/s00402-021-03838-8. Online ahead of print.PMID: 33649913
  41. Static and dynamic sagittal lumbar apex: a new concept for the assessment of lumbar lordosis distribution in spinal deformity Chizuo Iwai, Javier Pizones, Louis Boissière, Sreenath Jakinapally, Çaglar Yilgor, Daniel Larrieu, Ferran Pellise, Jean Marc Vital,Anouar Bourghli, Ibrahim Obeid European Spine Journal (2021)May;30(5):1155-1163.
  42. Isolated musculocutaneous neuropathy after posterior spine surgery for a patient with a subset of Marfan syndrome: A case report Chizuo Iwai, Kazunari Fushimi, Satoshi Nozawa, Shingo Komura, Shutaro Sawada, Hiroyasu Ogawa, Haruhiko Akiyama Interdisciplinary Neurosurgery: Advanced Techniques and Case Management (2021) https://doi.org/10.1016/j.inat.2021.101440
  43. Shimokawa T, Miyamoto K, Hioki A, Masuda T, Fushimi K, Ogawa H, Ohnishi K, Akiyama H. Compensatory Pelvic Retro-Rotation Associated with a Decreased Quality of Life in Patients with Normal Sagittal Balance. Asian Spine J. 2021 May 11. doi: 10.31616/asj.2020.0449.
  44. Hirakawa A, Komura S, Masuda T, Matsumoto K, Akiyama H. Destructive Arthropathy of the Interphalangeal Joint Following Revascularization After Degloving Hand Injury: A Case Report.Hand (N Y). 2021 Apr 1:15589447211003174. doi: 10.1177/15589447211003174.
  45. Miyagawa T, Matsumoto K, Komura S, Akiyama H. Total hip arthroplasty using a three-dimensional porous titanium acetabular cup: an examination of micromotion using subject-specific finite element analysis.BMC Musculoskelet Disord. 2021 Mar 26;22(1):308. doi: 10.1186/s12891-021-04174-z.
  46. Usui D, Komura S, Hirakawa A, Ichikawa K, Matsumoto K, Akiyama H. Corrective Surgery for a Forearm Deformity in a Middle-Aged Patient with Multiple Hereditary Exostoses: A Case Report. JBJS Case Connect. 2021 Jun 8;11(2).doi: 10.2106/JBJS.CC.20.00875.
  47. Kuroda Y, Tanaka T, Miyagawa T, Hamada H, Abe H, Ito-Ihara T, Asada R, Fujimoto Y, Takahashi D, Tetsunaga T, Kaneuji A, Takagi M, Inaba Y, Morita S, Sugano N, Tanaka S, Matsuda S, Akiyama H; TRION trial collaborators:. Recombinant human FGF-2 for the treatment of early-stage osteonecrosis of the femoral head: TRION, a single-arm, multicenter, Phase II trial. Regen Med. 2021 Jun 2. doi: 10.2217/rme-2021-0049. Online ahead of print.
  48. Asada R, Abe H, Hamada H, Fujimoto Y, Choe H, Takahashi D, Ueda S, Kuroda Y, Miyagawa T, Yamada K, Tanaka T, Ito J, Morita S, Takagi M, Tetsunaga T, Kaneuji A, Inaba Y, Tanaka S, Matsuda S, Sugano N, Akiyama H. Femoral head collapse rate among Japanese patients with pre-collapse osteonecrosis of the femoral head. J Int Med Res. 2021 Jun;49(6):3000605211023336. doi: 10.1177/03000605211023336.
  49. Kawashima K, Sugaya H, Takahashi N, Matsuki K, Takeuchi Y, Terabayashi N, Akiyama H. Relationship between the morphology of the greater tuberosity and radiological and clinical outcomes after arthroscopic rotator cuff repair. JSES Int. 2021 Jan 25;5(3):493-499. doi: 10.1016/j.jseint.2020.11.009. eCollection 2021 May.
  50. Kato K, Ogawa H, Matsumoto K, Akiyama H. Surgical procedures for the prevention of extension-flexion gap imbalance in total knee arthroplasty. J Orthop. 2021 May 14;25:224-229. doi: 10.1016/j.jor.2021.05.023. eCollection 2021 May-Jun.
  51. Akatsuka S, Matsumoto K, Ogawa H, Akiyama H. An unusual case report of tenosynovial giant cell tumor after unicompartmental knee arthroplasty presenting with recurrent hemarthrosis. J Orthop Sci. 2021 May 23:S0949-2658(21)00136-6. doi: 10.1016/j.jos.2021.03.019.
  52. Hirakawa A, Komura S, Nohara M, Masuda T, Matsushita Y, Akiyama H. Opponensplasty by the Palmaris Longus Tendon to the Rerouted Extensor Pollicis Brevis Transfer With Endoscopic Carpal Tunnel Release in Severe Carpal Tunnel Syndrome. J Hand Surg Am. 2021 May 22:S0363-5023(21)00212-4. doi: 10.1016/j.jhsa.2021.04.007.
  53. The 'other' bone sarcomas in Japan: a retrospective study of primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, using data from the Bone Tumuor Registry in Japan. Nagano A, Tsugita M, Nishimoto Y, Akiyama H, Kawai A. Jpn J Clin Oncol. 2021 Aug 30;51(9):1430-1436. doi: 10.1093/jjco/hyab090. PMID: 34105731
  54. Hirakawa A, Komura S, Nohara M, Shimizu T, Matsumoto K, Akiyama H. Collateral Ligament Reconstruction of a Distal Interphalangeal Joint with Chronic Instability: A Case Report. JBJS Case Connect. 2021 Oct 6;11(4). doi: 10.2106/JBJS.CC.21.00120.
  55. Komura S, Hirakawa A, Hirose H, Yamamoto K, Matsushita Y, Matsumoto K, Akiyama H. Reconstruction of a severe comminuted distal radius fracture with a large segmental bone defect by dorsal bridge plating combined with a vascularized fibular graft: A case report. J Orthop Sci. 2021 Sep 7:S0949-2658(21)00269-4. doi: 10.1016/j.jos.2021.08.003.
  56. Kawashima K, Terabayashi N, Asano H, Akiyama H. Total Shoulder Arthroplasty in a Patient with Nail-Patella Syndrome: A Case Report. JBJS Case Connect. 2021 Sep 2;11(3). doi: 10.2106/JBJS.CC.21.00138.
  57. Takeuchi K, Ogawa H, Kuramitsu N, Akaike K, Goto A, Aoki H, Lassar A, Suehara Y, Hara A, Matsumoto K, Akiyama H. Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.Osteoarthritis Cartilage. 2021 Aug 20:S1063-4584(21)00868-2. doi: 10.1016/j.joca.2021.08.001. Online ahead of print.PMID: 34425229
  58. Ichikawa K, Ogawa H, Matsumoto K, Akiyama H. Osteochondral Peg Fixation for Chondral Fragment of the Knee in Adolescent Patients: A Report of Two Cases.Case Rep Orthop. 2021 Jul 8;2021:9958012. doi: 10.1155/2021/9958012. eCollection 2021.
  59. Nagano A, Tsugita M, Nishimoto Y, Akiyama H, Kawai A. The 'other' bone sarcomas in Japan: a retrospective study of primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, using data from the Bone Tumuor Registry in Japan.Jpn J Clin Oncol. 2021 Aug 30;51(9):1430-1436. doi: 10.1093/jjco/hyab090.
  60. Komura S, Hirakawa A, Masuda T, Nohara M, Kimura A, Matsushita Y, Matsumoto K, Akiyama H. Preoperative prognostic factors associated with poor early recovery after trapeziectomy with ligament reconstruction and tendon interposition arthroplasty for thumb carpometacarpal osteoarthritis. Orthop Traumatol Surg Res. 2021 Dec 21:103191. doi: 10.1016/j.otsr.2021.103191. Online ahead of print.PMID: 34952216
  61. Takagi K, Nagano A, Tsugita M, Nishimoto Y, Miyazaki T, Akiyama H. Spontaneous Regression of Multiple Pulmonary Metastasis of Sacral Chordoma: A Case Report. JBJS Case Connect. 2021 Nov 22;11(4). doi: 10.2106/JBJS.CC.21.00227.
  62. Iwai C, Fushimi K, Nozawa S, Kato K, Miyagawa T, Takigami I, Akiyama H. Surgical Management of Thoracolumbar Scoliosis Secondary to Hip Joint Ankylosis and Severe Pelvic Obliquity. Cureus. 2021 Nov 19;13(11):e19744. doi: 10.7759/cureus.19744. eCollection 2021 Nov.PMID: 34938622
  63. Takagi K, Nagano A, Tsugita M, Nishimoto Y, Miyazaki T, Akiyama H. JBJS Case Connect. 2021 Nov 22;11(4). doi: 10.2106/JBJS.CC.21.00227. PMID: 34807890
  64. Nozawa S, Kato H, Kawaguchi M, Nozawa A, Yamada K, Iwai C, Fushimi K, Miyamoto K, Hosoe H, Shimizu K, Matsuo M, Akiyama H. Ectopic gas in the fibular graft after anterior cervical corpectomy and fusion. BMC Musculoskelet Disord. 2021 Nov 29;22(1):995.
  65. Ogawa H, Nakamura Y, Sengoku M, Shimokawa T, Sohmiya K, Ohnishi K, Matsumoto K, Akiyama H. Medial proximal tibial angle at the posterior tibial plateau represents the pre-arthritic constitutional medial proximal tibial angle in anterior cruciate ligament-intact, advanced osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2022 Jan 27. doi: 10.1007/s00167-022-06890-y. Online ahead of print.PMID: 35088097
  66. Ogawa H, Matsumoto K, Akiyama H. Repair of Osteochondritis Dissecans of the Lateral Femoral Condyle by a Trochlea Osteochondral Autograft: A Case Report. JBJS Case Connect. 2022 Jan 20;12(1). doi: 10.2106/JBJS.CC.21.00570.PMID: 35050965
  67. Okuda R, Hirakawa A, Komura S, Terabayashi N, Matsumoto K, Akiyama H. Heterotopic ossification of the elbow exacerbated by revision surgery for ipsilateral proximal humeral fracture: A case report. J Orthop Sci. 2022 Mar 26:S0949-2658(22)00066-5. doi: 10.1016/j.jos.2022.03.001. Online ahead of print.
  68. Current management of giant-cell tumor of bone in the denosumab era. Nagano A, Urakawa H, Tanaka K, Ozaki T. Jpn J Clin Oncol. 2022 May 5;52(5):411-416. doi: 10.1093/jjco/hyac018. PMID: 35199172
  69. Nakamura Y, Ogawa H, Sohmiya K, Sengoku M, Shimokawa T, Ohnishi K, Matsumoto K, Akiyama H. Relationship between histological changes of the anterior cruciate ligament and knee function in osteoarthritis patients.Orthop Traumatol Surg Res. 2022 May 25:103341. doi: 10.1016/j.otsr.2022.103341. Online ahead of print.
  70. Kato K, Miyamoto K, Shimizu K, Yozawa S, Ishii M, Akiyama H. A Rare Case of Cervical Myelopathy Caused by an Anomaly of the Axis: A Case Report and a Review of Current Comprehensive Literature. J Orthop Case Rep. 2022 Jan;12(1):54-57. doi: 10.13107/jocr.2022.v12.i01.2616.
  71. Ogawa H, Sengoku M, Shimokawa T, Nakamura Y, Ohnishi K, Matsumoto K, Akiyama H. Extra-articular factors of the femur and tibia affecting knee balance in mechanically aligned total knee arthroplasty.Orthop Traumatol Surg Res. 2022 May 1:103297. doi: 10.1016/j.otsr.2022.103297. Online ahead of print.
  72. Kawashima K, Terabayashi N, Asano H, Akiyama H. Arthroscopic Long Head of the Biceps Transposition for Superior Capsular Augmentation Results in Comparable Clinical Outcomes to Arthroscopic Partial Repair for Irreparable Rotator Cuff Tears.Arthrosc Sports Med Rehabil. 2021 Dec 23;4(2):e425-e434. doi: 10.1016/j.asmr.2021.10.020. eCollection 2022 Apr.
  73. Goto A, Iwata T, Nozawa S, Akiyama H. Humeral Diaphyseal Osteolytic Lesion as the Initial Presentation of Acute Myeloid Leukemia in a Child: A Case Report and Review of the Literature.Cureus. 2022 Mar 3;14(3):e22791. doi: 10.7759/cureus.22791. eCollection 2022 Mar.
  74. Yoshioka H, Komura S, Kuramitsu N, Goto A, Hasegawa T, Amizuka N, Ishimoto T, Ozasa R, Nakano T, Imai Y, Akiyama H. Deletion of Tfam in Prx1-Cre expressing limb mesenchyme results in spontaneous bone fractures. J Bone Miner Metab. 2022 Aug 10. doi: 10.1007/s00774-022-01354-2.
  75. Sohmiya K, Ogawa H, Nakamura Y, Sengoku M, Shimokawa T, Ohnishi K, Akiyama H. Joint gap produced by manual stress is dependent on the surgeon's experience and is smaller in flexion in robotic-assisted total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2022 Aug 15. doi: 10.1007/s00167-022-07107-y.
  76. Ogawa H, Nakamura Y, Sengoku M, Shimokawa T, Sohmiya K, Ohnishi K, Matsumoto K, Akiyama H. Thinner tuberosity osteotomy is more resistant to axial load in medial open-wedge distal tuberosity proximal tibial osteotomy: A biomechanical study.Knee. 2022 Aug 2;38:62-68. doi: 10.1016/j.knee.2022.07.010. Online ahead of print.PMID: 35930894
  77. Satake T, Komura S, Aoki H, Hirakawa A, Imai Y, Akiyama H. Induction of iPSC-derived Prg4-positive cells with characteristics of superficial zone chondrocytes and fibroblast-like synovial cells.BMC Mol Cell Biol. 2022 Jul 23;23(1):30. doi: 10.1186/s12860-022-00431-8.
  78. Nakamura Y, Saitou M, Komura S, Matsumoto K, Ogawa H, Miyagawa T, Saitou T, Imamura T, Imai Y, Takayanagi H, Akiyama H. Reduced dynamic loads due to hip dislocation induce acetabular cartilage degeneration by IL-6 and MMP3 via the STAT3/periostin/NF-κB axis. Sci Rep. 2022 Jul 16;12(1):12207. doi: 10.1038/s41598-022-16585-6.
  79. Asano H, Terabayashi N, Kawashima K, Goto A, Watanabe T, Ishihara T, Akiyama H. Blood flow in the anterior humeral circumflex artery reflects synovial inflammation of the shoulder joint in rotator cuff tears.JSES Int. 2022 May 6;6(4):623-630. doi: 10.1016/j.jseint.2022.04.006. eCollection 2022 Jul.
  80. Matsumoto K, Ogawa H, Komura S, Akiyama H. Functional Impairment of Hip Joint and Activities of Daily Living Failure in Patients with Multiple Hereditary Exostoses. Indian J Orthop. 2022 Jul 28;56(9):1572-1577. doi: 10.1007/s43465-022-00681-w. eCollection 2022 Sep.
  81. Nagano A, Urakawa H, Tanaka K, Ozaki T. Current management of giant-cell tumor of bone in the denosumab era. Jpn J Clin Oncol. 2022 May 5;52(5):411-416. doi: 10.1093/jjco/hyac018.
  82. Phosphoglyceride Crystal Deposition Disease of the Scapula: A Case Report and Literature Review. Hori Y, Nagano A, Miyazaki T, Kato H, Tsugita M, Nishimoto Y, Akiyama H. JBJS Case Connect. 2023 Jan 19;13(1). doi: 10.2106/JBJS.CC.22.00520. eCollection 2023 Jan 1.PMID: 36656996
  83. Trapeziectomy with ligament reconstruction and tendon interposition arthroplasty continuously improves hand functions up to 5-year postoperatively. Komura S, Hirakawa A, Hirose H, Akiyama H.Arch Orthop Trauma Surg. 2023 Jan 21. Online ahead of print.
  84. First Dorsal Metacarpal Artery-pedicled Second Metacarpal Vascularized Bone Graft for Nonunion after Thumb Carpometacarpal Arthrodesis. Komura S, Hirakawa A, Hirose H, Akiyama H. Plast Reconstr Surg Glob Open. 2023 Mar 16;11(3):e4882.
  85. Comparison of Surgical Outcomes for Arthrodesis and Arthroplasty for Thumb Carpometacarpal Osteoarthritis in Female Workers Komura S, Hirakawa A, Hirose H, Akiyama H. Journal of Hand and Microsurgery.22 May 2023. Online ahead of print.
  86. C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis. Goto A, Komura S, Kato K, Maki R, Hirakawa A, Tomita H, Hirata A, Yamada Y, Akiyama H. Commun Biol. 2023 Nov 18;6(1):1173. doi: 10.1038/s42003-023-05558-8.
  87. Two-stage reconstruction using a vancomycin-impregnated cement spacer for finger osteomyelitis with bone and joint destruction. Okumura T, Komura S, Hirakawa A, Hirose H, Akiyama H. Hand Surg Rehabil. 2024 Feb;43(1):101602. doi: 10.1016/j.hansur.2023.09.369.
  88. Minimally invasive arthroscopy-assisted arthrodesis for thumb carpometacarpal osteoarthritis. Komura S, Hirakawa A, Hirose H, Akiyama H. Arch Orthop Trauma Surg. 2024 Feb;144(2):967-974. doi: 10.1007/s00402-023-05145-w.
  89. Surgical Management of Intraosseous Neurofibroma in Cervical Spine A Case Report JBJS Case Connect (2024) C.Iwai, S.Nozawa, K.Fushimi, K.Yamada, H.Akiyama,
  90. Surgical Management of omega deformity in a patient with neurofibromatosis type1: A Case Report European Spine Journal (2024) C.Iwai, S.Nozawa, K.Fushimi, K.Yamada, H.Akiyama,