臨床整形外科52巻7号

2017年07月発行

最新基礎科学/知っておきたい

新規変形性関節症治療の現状と展望

著者： 松下雄彦¹ 西田京平¹ 田中聡一¹ 宮地伸晃¹ 茨木一行¹

所属機関： ¹神戸大学大学院医学研究科・外科系講座・整形外科学

ページ範囲：P.654 - P.658

はじめに

　変形性関節症(OA)は軟骨の変性や摩耗に伴って進行していく疾患であるが，いまだ，OA進行を抑制する薬剤や治療は確立されていない．OAの発症や病態にはさまざまな因子が関わっていることが示唆されており，その病態に介入する研究が行われている．また，その一方で近年では細胞治療も報告されており，さまざまな方面から治療のアプローチがなされてきている．本章では，OAの病態や新規OA治療薬の開発に向けた臨床的な研究の一部を紹介する．

参考文献

1) Little CB, Barai A, Burkhardt D, et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009;60:3723-33.

2) Krzeski P, Buckland-Wright C, Bálint G, et al. Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis:a randomized, 12-month, double-blind, placebo-controlled study. Arthritis Res Ther 2007;9:R109.

3) Baragi VM, Becher G, Bendele AM, et al. A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis:Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models. Arthritis Rheum 2009;60:2008-18.

4) Stanton H, Rogerson FM, East CJ, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 2005;434:648-52.

5) Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005;434:644-8.

6) Buckland-Wright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthritis Cartilage 2004;12 Suppl A:S10-9.

7) Hayami T, Pickarski M, Zhuo Y, et al. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 2006;38:234-43.

8) Hayami T, Pickarski M, Wesolowski GA, et al. The role of subchondral bone remodeling in osteoarthritis:reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum 2004;50:1193-206.

9) Shirai T, Kobayashi M, Nishitani K, et al. Chondroprotective effect of alendronate in a rabbit model of osteoarthritis. J Orthop Res 2011;29:1572-7.

10) Davis AJ, Smith TO, Hing CB, et al. Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review. PLoS One 2013;8:e72714.

11) Xing RL, Zhao LR, Wang PM. Bisphosphonates therapy for osteoarthritis:a meta-analysis of randomized controlled trials. Springerplus 2016;5:1704.

12) Moore EE, Bendele AM, Thompson DL, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 2005;13:623-31.

13) Sekiya I, Tang T, Hayashi M, et al. Periodic knee injections of BMP-7 delay cartilage degeneration induced by excessive running in rats. J Orthop Res 2009;27:1088-92.

14) Dahlberg LE, Aydemir A, Muurahainen N, et al. A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis. Clin Exp Rheumatol 2016;34:445-50.

15) Hunter DJ, Pike MC, Jonas BL, et al. Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskelet Disord 2010;11:232.

16) Filardo G, Di Matteo B, Di Martino A, et al. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation:A randomized controlled trial. Am J Sports Med 2015;43:1575-82.

17) Cole BJ, Karas V, Hussey K, et al. Hyaluronic acid versus platelet-rich plasma:a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med 2017;45:339-46.

18) Meheux CJ, McCulloch PC, Lintner DM, et al. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis:a systematic review. Arthroscopy 2016;32:495-505.

19) Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.

20) Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies. Tissue Eng 2001;7:211-28.

21) De Bari C, Dell'Accio F, Tylzanowski P, et al. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001;44:1928-42.

22) Nejadnik H, Hui JH, Feng Choong EP, et al. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation:an observational cohort study. Am J Sports Med 2010;38:1110-6.

23) Koh YG, Jo SB, Kwon OR, et al. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 2013;29:748-55.

24) Vangsness CT Jr, Farr J 2nd, Boyd J, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy:a randomized, double-blind, controlled study. J Bone Joint Surg Am 2014;96:90-8.

25) Kim YS, Choi YJ, Suh DS, et al. Mesenchymal stem cell implantation in osteoarthritic knees:is fibrin glue effective as a scaffold? Am J Sports Med 2015;43:176-85.

26) Kim YS, Choi YJ, Koh YG. Mesenchymal stem cell implantation in knee osteoarthritis:an assessment of the factors influencing clinical outcomes. Am J Sports Med 2015;43:2293-301.

27) Pers YM, Rackwitz L, Ferreira R, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee:a phase i dose-escalation trial. Stem Cells Transl Med 2016;5:847-56.

28) Michalek J, Moster R, Lukac L, et al. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant 2015 Jan 20. (Epub ahead of print)