运动性软骨损伤的问题及潜在性治疗方案
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摘要
背景:关节软骨损伤在运动中非常普遍,主要由慢性关节应力或急性创伤性扭伤引起,往往会导致关节功能进行性损害,并限制相关运动和锻炼的参与。现有的关节软骨修复技术可以修复高冲击运动所致的关节软骨损伤,但这种治疗方法不产生正常的关节软骨,限制了软骨修复的成功率和耐久性。目的:综述近年国内外治疗运动性软骨损伤中出现的问题及潜在性的治疗进展。方法:以"运动""软骨""回顾""治疗"为中文关键词,在中国知网、维普、万方等中文数据库进行检索,并以"cartilage""exercise""review""back pain""treat"作为外文关键词,在PubMed、Google Scholar、Web of Science等数据库进行检索,重点筛选近5年的文献,检索文献语种为中文和英文。共检得文献627篇,依据纳入和排除标准,最终纳入相关文献44篇。结果与结论:(1)治疗运动性关节软骨损伤的目标是减少疼痛,改善膝关节功能,最重要的是让运动员恢复到受伤前的运动水平;(2)目前已有一些手术技术已经实现可变耐用的关节软骨修复,让运动员重返体育运动和锻炼,然而手术不会产生完全正常的透明软骨;(3)研究发现,关节软骨中存在软骨祖细胞,具有迁移行为、多分化能力和克隆形成性,由于不同性质和程度的机械损伤刺激软骨祖细胞,导致凋亡0细胞释放化学引诱物,从而分化成软骨原细胞,修复损伤软骨;(4)基于此,生物打印富含软骨祖细胞的特异性骨软骨结构,以替代受损关节仍是未来的潜在性战略方案。
BACKGROUND: Articular cartilage damage is very common in exercise and is mainly caused by chronic joint stress or acute traumatic sprain, which often leads to progressive damage of joint function and limits the participation of related exercise and exercise. The existing articular cartilage repair technique can repair articular cartilage damage caused by high impact exercise, but this treatment cannot produce normal articular cartilage, which limits the success rate and durability of cartilage repair.OBJECTIVE: To review the problems and potential treatment progress in the treatment of sports cartilage injury at home and abroad in recent years.METHODS: CNKI, VIP, WanFang, PubMed, Google Scholar, and Web of Science databases were retrieved using the keywords of "cartilage,exercise, review, back pain, treat" in Chinese and English, respectively, focusing on the selection of literature published in the past 5 years. A total of 627 articles were searched, and 44 eligible articles were included based on inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1) The goal of treating sports articular cartilage injury is to alleviate pain, improve knee function, and most importantly, to restore athletes to the level of exercise before injury.(2) At present, some surgical techniques have been implemented to achieve variable and durable articular cartilage repair, allowing athletes to return to sports and exercise. However, surgery does not produce completely normal hyaline cartilage.(3) It has been found that cartilage progenitor cells exist in articular cartilage, and have migration behavior, multi-differentiation ability and colony formation ability. Because mechanical injuries with different characteristics and intensities simulate cartilage progenitor cells, so apoptotic cells release inducers, thus differentiating into chondroblasts to repair injured cartilage.(4)Thereafter, bioprinting of specific osteochondral structures rich in cartilage progenitor cells to replace damaged joints remains a potential strategy in the future.
BACKGROUND: Articular cartilage damage is very common in exercise and is mainly caused by chronic joint stress or acute traumatic sprain, which often leads to progressive damage of joint function and limits the participation of related exercise and exercise. The existing articular cartilage repair technique can repair articular cartilage damage caused by high impact exercise, but this treatment cannot produce normal articular cartilage, which limits the success rate and durability of cartilage repair.OBJECTIVE: To review the problems and potential treatment progress in the treatment of sports cartilage injury at home and abroad in recent years.METHODS: CNKI, VIP, WanFang, PubMed, Google Scholar, and Web of Science databases were retrieved using the keywords of "cartilage,exercise, review, back pain, treat" in Chinese and English, respectively, focusing on the selection of literature published in the past 5 years. A total of 627 articles were searched, and 44 eligible articles were included based on inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1) The goal of treating sports articular cartilage injury is to alleviate pain, improve knee function, and most importantly, to restore athletes to the level of exercise before injury.(2) At present, some surgical techniques have been implemented to achieve variable and durable articular cartilage repair, allowing athletes to return to sports and exercise. However, surgery does not produce completely normal hyaline cartilage.(3) It has been found that cartilage progenitor cells exist in articular cartilage, and have migration behavior, multi-differentiation ability and colony formation ability. Because mechanical injuries with different characteristics and intensities simulate cartilage progenitor cells, so apoptotic cells release inducers, thus differentiating into chondroblasts to repair injured cartilage.(4)Thereafter, bioprinting of specific osteochondral structures rich in cartilage progenitor cells to replace damaged joints remains a potential strategy in the future.
引文
[1]Flanigan DC,Harris JD,Trinh TQ,et al.Prevalence of chondral defects in athletes’knees:a systematic review.Med Sci Sports Exerc.2010;42:1795-1801.
[2]Heijink A,Gomoll AH,Madry H,et al.Biomechanical considerations in the pathogenesis of osteoarthritis of the knee.Knee Surg Sports Traumatol Arthrosc.2012;20(3):423-435.
[3]Jones G,Bennell K,Cicuttini FM.Effect of physical activity on cartilage development in healthy kids.Br J Sports Med.2003;37:382-383.
[4]Goldring MB,Berenbaum F.Emerging Targets in Osteoarthritis Therapy.Curr Opin Pharmacol.2015;22:51-63.
[5]Malfait A-M,Schnitzer TJ.Towards a mechanism-based approach to pain management in osteoarthritis.Nat rev Rheumatol.2013;9(11):654-664.
[6]Gobbi A,Karnatzikos G,Kumar A.Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes.Knee Surg Sports Traumatol Arthrosc.2014;22:1986-1996.
[7]Kon E,Filardo G,Berruto M,et al.Articular cartilage treatment in high-level male soccer players:a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantationversus microfracture.Am J Sports Med.2011;39:2549-2557.
[8]Ekstrand J,H?gglund M,Kristenson K,et al.Fewer ligament injuries but no preventive effect on muscle injuries and severe injuries:an 11-year follow-up of the UEFA Champions League injury study.Br J Sports Med.2013;47:732-737.
[9]Torrie AM,Kesler WW,Elkin J,et al.Osteochondral allograft.Curr Rev Musculoskelet Med.2015;8(4):413-422.
[10]Marcacci M,Kon E,Delcogliano M,et al.Arthroscopic autologous osteochondral grafting for cartilage defects of the knee:prospective study results at a minimum 7-year follow-up.Am J Sports Med.2007;35:2014-2021.
[11]Mithoefer K,Peterson L,Zenobi-Wong M,et al.Cartilage issues in football-today’s problems and tomorrow’s solutions.Br J Sports Med.2015;49(9):590-596.
[12]Krych AJ,Robertson CM,Williams RJ III.Return to athletic activity after osteochondral allograft transplantation in the knee.Am J Sports Med.2012;40:1053-1059.
[13]Hindle P,Hendry JL,Keating JF,et al.Autologous osteochondral mosaicplasty or TruFit?plugs for cartilage repair.Knee Surg Sports Traumatol Arthrosc.2014,22:1235-1240.
[14]Brittberg M,Lindahl A,Nilsson A,et al.Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.N Engl J Med.1994;331:889-895.
[15]Peterson L,Vasiliadis HS,Brittberg M,et al.Autologous chondrocyte implantation:a long-term follow-up.Am J Sports Med.2010;38:1117-1124.
[16]Vasiliadis HS,Danielson B,Ljungberg M,et al.Autologous chondrocyte implantation in cartilage lesions of the knee:long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.Am J Sports Med.2010;38:943-949.
[17]Mithoefer K,Peterson L,Saris DBF,et al.Evolution and current role of autologous chondrocyte transplantation for the treatment of articular cartilage defects in the football(soccer)player.Cartilage.2012;3(1 Suppl):31S-36S.
[18]Mith?fer K,Minas T,Peterson L,et al.Functional outcome of articular cartilage repair in adolescent athletes.Am J Sports Med.2005;33:1147-1153.
[19]Della Villa S,Kon E,Filardo G,et al.Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes?Am J Sports Med.2010;38:68-77.
[20]Bartlett W,Skinner JA,Gooding CR,et al.Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee:a prospective,randomized study.J Bone Joint Surg Br.2005;87:640-645.
[21]Almonte-Becerril M,Gimeno-LLuch I,Villarroya O,et al.Genetic abrogation of the fibronectin-α5β1 integrin interaction in articular cartilage aggravates osteoarthritis in mice.PLoSOne.2018;13(6):e0198559.
[22]Wondrasch B,Risberg MA,Zak L,et al.Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle:a prospective,randomized controlled study presenting MRI-based and clinical outcomes after 5 years.Am J Sports Med.2015;43:146-153.
[23]Ebert JR,Fallon M,Zheng MH,et al.A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation:findings at 5 years.Am J Sports Med.2012;40:1527-1537.
[24]Harris JD,Brophy RH,Siston RA,et al.Treatment of chondral defects in the athlete's knee.Arthroscopy.2010;26:841-852.
[25]Ebert JR,Smith A,Edwards PK,et al.Factors predictive of outcome 5 years after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint.Am J Sports Med.2013;41:1245-1254.
[26]Mithoefer K,Hambly K,Della Villa S,et al.Return to sports participation after articular cartilage repair in the knee:scientific evidence.Am J Sports Med.2009;37(Suppl 1):167S-76S.
[27]Foster TE,Puskas BL,Mandelbaum BR,et al.Platelet-rich plasma:from basic science to clinical applications.Am JSports Med.2009;37:2259-2272.
[28]Kon E,Mandelbaum B,Buda R,et al.Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology:from early degeneration to osteoarthritis.Arthroscopy.2011;27:1490-1501.
[29]Sanchez M,Fiz N,Azofra J,et al.A randomized clinical trial evaluating plasma rich in growth factors(PRGF-Endoret)versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.J Arthroscopy.2012;28:1070-1078.
[30]Morisset S,Frisbee DD,Robbins PD,et al.Il-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.Clin Orthop Relat Res.2007;462:221-228.
[31]Neumann K,Dehne T,Endres M,et al.Chodrogenic differentiation capacity of human mesenchymal progenitor cells derived from subchondral corticospongious bone.JOrthop Res.2008;26:1449-1456.
[32]Gille J,Schuseil E,Wimmer J,et al.Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee.Knee Surg Sports Traumatol Arthrosc.2010;18:1456-1464.
[33]Stanish WD,McCormack R,Forriol F,et al.Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial.J Bone Joint Surg Am.2013;95:1640-1650.
[34]Gobbi A,Karnatzikos G,Sankineani SR.One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee.Am J Sports Med.2014;42:648-657.
[35]Farr J,Tabet SK,Margerrison E,et al.Clinical,radiographic,and histological outcomes after cartilage repair with particulated juvenile articular cartilage:a 2-year prospective study.Am J Sports Med.2014;42:1417-1425.
[36]Jiang Y,Tuan RS.Origin and function of cartilage stem/progenitor cells in osteoarthritis.Nat Rev Rheumatol.2014;10:1038.
[37]Seol D,MaCabe DH,Choe D,et al.Chondrogenic progenitor cells respond to cartilage injury.Arthritis Rheum.2012;64:3626-3637.
[38]Bos PK,Kops N,Verhaar JA,et al.Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment.Osteoarthritis Cartilage.2008;16:204-211.
[39]Grogan SP,Miyaki S,Asahara H,et al.Mesenchymal progenitor cell markers in human articular cartilage:normal distribution and changes in osteoarthritis.Arthritis Res Ther.2009;11:R85.
[40]Burdick JA,Mauck RL,Gorman JH,et al.Acellular biomaterials:an evolving alternative to cell-based therapies.Sci Transl Med.2013;5:176-174
[41]Yu Y,Brouillette MJ,Seol D,et al.Functional full-thickness articular cartilage repair by rhSDF-1alpha loaded fibrin/ha hydrogel network via chondrogenic progenitor cells homing.Arthritis Rheumatol.2015;10:1002.
[42]Mhanna R,Ozturk E,Vallmajo-Martin Q,et al.GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic differentiation of human mesenchymal stem cells.Tissue Eng Part A.2014;20:1165-1174.
[43]Lee CH,Cook JL,Mendelson A,et al.Regeneration of the articular surface of the rabbit synovial joint by cell homing:a proof of concept study.Lancet.2010;376:440-448.
[44]Luria A,Chu CR.Articular cartilage changes in maturing athletes:new targets for joint rejuvenation.Sports Health.2014,6(1):18-30.
[2]Heijink A,Gomoll AH,Madry H,et al.Biomechanical considerations in the pathogenesis of osteoarthritis of the knee.Knee Surg Sports Traumatol Arthrosc.2012;20(3):423-435.
[3]Jones G,Bennell K,Cicuttini FM.Effect of physical activity on cartilage development in healthy kids.Br J Sports Med.2003;37:382-383.
[4]Goldring MB,Berenbaum F.Emerging Targets in Osteoarthritis Therapy.Curr Opin Pharmacol.2015;22:51-63.
[5]Malfait A-M,Schnitzer TJ.Towards a mechanism-based approach to pain management in osteoarthritis.Nat rev Rheumatol.2013;9(11):654-664.
[6]Gobbi A,Karnatzikos G,Kumar A.Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes.Knee Surg Sports Traumatol Arthrosc.2014;22:1986-1996.
[7]Kon E,Filardo G,Berruto M,et al.Articular cartilage treatment in high-level male soccer players:a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantationversus microfracture.Am J Sports Med.2011;39:2549-2557.
[8]Ekstrand J,H?gglund M,Kristenson K,et al.Fewer ligament injuries but no preventive effect on muscle injuries and severe injuries:an 11-year follow-up of the UEFA Champions League injury study.Br J Sports Med.2013;47:732-737.
[9]Torrie AM,Kesler WW,Elkin J,et al.Osteochondral allograft.Curr Rev Musculoskelet Med.2015;8(4):413-422.
[10]Marcacci M,Kon E,Delcogliano M,et al.Arthroscopic autologous osteochondral grafting for cartilage defects of the knee:prospective study results at a minimum 7-year follow-up.Am J Sports Med.2007;35:2014-2021.
[11]Mithoefer K,Peterson L,Zenobi-Wong M,et al.Cartilage issues in football-today’s problems and tomorrow’s solutions.Br J Sports Med.2015;49(9):590-596.
[12]Krych AJ,Robertson CM,Williams RJ III.Return to athletic activity after osteochondral allograft transplantation in the knee.Am J Sports Med.2012;40:1053-1059.
[13]Hindle P,Hendry JL,Keating JF,et al.Autologous osteochondral mosaicplasty or TruFit?plugs for cartilage repair.Knee Surg Sports Traumatol Arthrosc.2014,22:1235-1240.
[14]Brittberg M,Lindahl A,Nilsson A,et al.Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.N Engl J Med.1994;331:889-895.
[15]Peterson L,Vasiliadis HS,Brittberg M,et al.Autologous chondrocyte implantation:a long-term follow-up.Am J Sports Med.2010;38:1117-1124.
[16]Vasiliadis HS,Danielson B,Ljungberg M,et al.Autologous chondrocyte implantation in cartilage lesions of the knee:long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.Am J Sports Med.2010;38:943-949.
[17]Mithoefer K,Peterson L,Saris DBF,et al.Evolution and current role of autologous chondrocyte transplantation for the treatment of articular cartilage defects in the football(soccer)player.Cartilage.2012;3(1 Suppl):31S-36S.
[18]Mith?fer K,Minas T,Peterson L,et al.Functional outcome of articular cartilage repair in adolescent athletes.Am J Sports Med.2005;33:1147-1153.
[19]Della Villa S,Kon E,Filardo G,et al.Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes?Am J Sports Med.2010;38:68-77.
[20]Bartlett W,Skinner JA,Gooding CR,et al.Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee:a prospective,randomized study.J Bone Joint Surg Br.2005;87:640-645.
[21]Almonte-Becerril M,Gimeno-LLuch I,Villarroya O,et al.Genetic abrogation of the fibronectin-α5β1 integrin interaction in articular cartilage aggravates osteoarthritis in mice.PLoSOne.2018;13(6):e0198559.
[22]Wondrasch B,Risberg MA,Zak L,et al.Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle:a prospective,randomized controlled study presenting MRI-based and clinical outcomes after 5 years.Am J Sports Med.2015;43:146-153.
[23]Ebert JR,Fallon M,Zheng MH,et al.A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation:findings at 5 years.Am J Sports Med.2012;40:1527-1537.
[24]Harris JD,Brophy RH,Siston RA,et al.Treatment of chondral defects in the athlete's knee.Arthroscopy.2010;26:841-852.
[25]Ebert JR,Smith A,Edwards PK,et al.Factors predictive of outcome 5 years after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint.Am J Sports Med.2013;41:1245-1254.
[26]Mithoefer K,Hambly K,Della Villa S,et al.Return to sports participation after articular cartilage repair in the knee:scientific evidence.Am J Sports Med.2009;37(Suppl 1):167S-76S.
[27]Foster TE,Puskas BL,Mandelbaum BR,et al.Platelet-rich plasma:from basic science to clinical applications.Am JSports Med.2009;37:2259-2272.
[28]Kon E,Mandelbaum B,Buda R,et al.Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology:from early degeneration to osteoarthritis.Arthroscopy.2011;27:1490-1501.
[29]Sanchez M,Fiz N,Azofra J,et al.A randomized clinical trial evaluating plasma rich in growth factors(PRGF-Endoret)versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.J Arthroscopy.2012;28:1070-1078.
[30]Morisset S,Frisbee DD,Robbins PD,et al.Il-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.Clin Orthop Relat Res.2007;462:221-228.
[31]Neumann K,Dehne T,Endres M,et al.Chodrogenic differentiation capacity of human mesenchymal progenitor cells derived from subchondral corticospongious bone.JOrthop Res.2008;26:1449-1456.
[32]Gille J,Schuseil E,Wimmer J,et al.Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee.Knee Surg Sports Traumatol Arthrosc.2010;18:1456-1464.
[33]Stanish WD,McCormack R,Forriol F,et al.Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial.J Bone Joint Surg Am.2013;95:1640-1650.
[34]Gobbi A,Karnatzikos G,Sankineani SR.One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee.Am J Sports Med.2014;42:648-657.
[35]Farr J,Tabet SK,Margerrison E,et al.Clinical,radiographic,and histological outcomes after cartilage repair with particulated juvenile articular cartilage:a 2-year prospective study.Am J Sports Med.2014;42:1417-1425.
[36]Jiang Y,Tuan RS.Origin and function of cartilage stem/progenitor cells in osteoarthritis.Nat Rev Rheumatol.2014;10:1038.
[37]Seol D,MaCabe DH,Choe D,et al.Chondrogenic progenitor cells respond to cartilage injury.Arthritis Rheum.2012;64:3626-3637.
[38]Bos PK,Kops N,Verhaar JA,et al.Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment.Osteoarthritis Cartilage.2008;16:204-211.
[39]Grogan SP,Miyaki S,Asahara H,et al.Mesenchymal progenitor cell markers in human articular cartilage:normal distribution and changes in osteoarthritis.Arthritis Res Ther.2009;11:R85.
[40]Burdick JA,Mauck RL,Gorman JH,et al.Acellular biomaterials:an evolving alternative to cell-based therapies.Sci Transl Med.2013;5:176-174
[41]Yu Y,Brouillette MJ,Seol D,et al.Functional full-thickness articular cartilage repair by rhSDF-1alpha loaded fibrin/ha hydrogel network via chondrogenic progenitor cells homing.Arthritis Rheumatol.2015;10:1002.
[42]Mhanna R,Ozturk E,Vallmajo-Martin Q,et al.GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic differentiation of human mesenchymal stem cells.Tissue Eng Part A.2014;20:1165-1174.
[43]Lee CH,Cook JL,Mendelson A,et al.Regeneration of the articular surface of the rabbit synovial joint by cell homing:a proof of concept study.Lancet.2010;376:440-448.
[44]Luria A,Chu CR.Articular cartilage changes in maturing athletes:new targets for joint rejuvenation.Sports Health.2014,6(1):18-30.