机械加载减轻骨关节炎小鼠的病理进展
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摘要
目的探讨机械加载对骨关节炎(OA)模型小鼠早、晚期OA的治疗作用。方法选用8周龄的C57BL/6雌性小鼠36只,按随机数字表法分为正常对照组(Control组)、OA组和OA机械加载治疗组(OAL组),每组又分为2周和8周亚组(n=6)。使用HE和番红O/快绿染色观察机械加载治疗对早、晚期OA小鼠软骨、滑膜和骨赘的治疗作用。结果与Control组相比,OA小鼠透明软骨(HC)厚度、全部关节软骨(TAC)厚度均变薄,国际骨关节炎研究学会(OARSI)评分、滑膜评分、骨赘评分均升高(均P<0.05)。机械加载治疗后,OAL组HC、TAC厚度均增加,OARSI评分、滑膜评分、骨赘评分均下降(均P<0.05)。相对数据表明,与早期OA小鼠相比,晚期小鼠的病理变化更严重,并且机械加载对晚期OA的治疗效果更好。相关性分析表明,OA早期软骨的退化可能与滑膜炎症有关,而晚期可能与骨赘形成有关。结论机械加载可以改善OA小鼠的病理改变,可以作为一种新型的临床治疗手段。
Objective To investigate the therapeutic effects of mechanical loading on early and late osteoarthritis(OA) of model mice.Methods Thirty-six 8-week-old female C57 BL/6 mice, weighing about 20 g, were divided into the normal control(Control) group, OA group, and OA+loading(OAL) group by a random number table method. Each group was subdivided into 2-week and 8-week sub-groups(n=6). H&E and Safranin O/fast green staining were used to evaluate the therapeutic effects of mechanical loading on cartilage, synovium and osteophyte in early and late OA mice.Results Compared with the Control group, the thickness of hyaline cartilage(HC) and the thickness of all articular cartilage(TAC)were thinner in OA mice, and the OARSI score, synovial score and osteophyte score were significantly increased(all P<0.05). After mechanical loading, the thickness of HC and TAC were increased in OAL group, and OARSI score, synovial score and osteophyte score were decreased(all P<0.05). The relative data suggested that pathological changes were more severe in mice with late OA compared with mice of early OA, and the therapeutic effect of mechanical loading was better for the late OA. Correlation analysis showed that the early cartilage degradation of OA may be related to the synovial inflammation, and the late stage of OA may be related to the osteophyte formation.Conclusion Mechanical loading can improve the pathological changes of osteoarthritis mice, indicating that mechanical loading can be used as a new type of clinical treatment for osteoarthritis.
Objective To investigate the therapeutic effects of mechanical loading on early and late osteoarthritis(OA) of model mice.Methods Thirty-six 8-week-old female C57 BL/6 mice, weighing about 20 g, were divided into the normal control(Control) group, OA group, and OA+loading(OAL) group by a random number table method. Each group was subdivided into 2-week and 8-week sub-groups(n=6). H&E and Safranin O/fast green staining were used to evaluate the therapeutic effects of mechanical loading on cartilage, synovium and osteophyte in early and late OA mice.Results Compared with the Control group, the thickness of hyaline cartilage(HC) and the thickness of all articular cartilage(TAC)were thinner in OA mice, and the OARSI score, synovial score and osteophyte score were significantly increased(all P<0.05). After mechanical loading, the thickness of HC and TAC were increased in OAL group, and OARSI score, synovial score and osteophyte score were decreased(all P<0.05). The relative data suggested that pathological changes were more severe in mice with late OA compared with mice of early OA, and the therapeutic effect of mechanical loading was better for the late OA. Correlation analysis showed that the early cartilage degradation of OA may be related to the synovial inflammation, and the late stage of OA may be related to the osteophyte formation.Conclusion Mechanical loading can improve the pathological changes of osteoarthritis mice, indicating that mechanical loading can be used as a new type of clinical treatment for osteoarthritis.
引文
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[13]Nakamura A,Rampersaud YR,Nakamura S,et al.Micro RNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints[J].Ann Rheum Dis,2019,78(11):111-121.doi:10.1136/annrheumdis-2018-213629.
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[15]Hamamura K,Zhang P,Zhao L,et al.Knee loading reduces MMP13 activity in the mouse cartilage[J].BMC Musculoskelet Disord,2013,14:312.doi:10.1186/1471-2474-14-312.
[16]Malfait AM.Osteoarthritis year in review 2015:biology[J].Osteoarthritis Cartilage,2016,24(1):21-26.doi:10.1016/j.joca.2015.09.010.
[17]Chinzei N,Rai MF,Hashimoto S,et al.Evidence for genetic contribution to variation in post-traumatic osteoarthritis in mice[J].Arthritis Rheumatol,2019,71(3):370-381.doi:10.1002/art.40730.
[18]Bechtold TE,Saunders C,Decker RS,et al.Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling[J].Matrix Biol,2016,52/53/54:339-354.doi:10.1016/j.matbio.2016.03.001.
[2]Huang Z,Ding C,Li T,et al.Current status and future prospects for disease modification in osteoarthritis[J].Rheumatology(Oxford),2018,57(suppl_4):iv108-iv123.doi:10.1093/rheumatology/kex496.
[3]Pereira D,Ramos E,Branco J.Osteoarthritis[J].Acta Med Port,2015,28(1):99-106.
[4]Schelbergen RF,de Munter W,van den Bosch MH,et al.Alarmins S100A8/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis[J].Ann Rheum Dis,2016,75(1):218-225.doi:10.1136/annrheumdis-2014-205480.
[5]Lieben L.Osteoarthritis:Osteophyte formation involves PAR2[J].Nat Rev Rheumatol,2016,12(2):70-71.doi:10.1038/nrrheum.2016.6.
[6]Wong SH,Chiu KY,Yan CH.Review article:osteophytes[J].JOrthop Surg(Hong Kong),2016,24(3):403-410.
[7]Fibel KH,Hillstrom HJ,Halpern BC.State-of-the-Art management of knee osteoarthritis[J].World J Clin Cases,2015,3(2):89-101.doi:10.12998/wjcc.v3.i2.89.
[8]Li X,Yang J,Liu D,et al.Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis[J].Sci Rep,2016,6:24668.doi:10.1038/srep24668.
[9]Wang Q,Tan QY,Xu W,et al.Cartilage-specific deletion of Alk5gene results in a progressive osteoarthritis-like phenotype in mice[J].Osteoarthritis Cartilage,2017,25(11):1868-1879.doi:10.1016/j.joca.2017.07.010.
[10]Zhang P,Tanaka SM,Sun Q,et al.Frequency-dependent enhancement of bone formation in murine tibiae and femora with knee loading[J].J Bone Miner Metab,2007,25(6):383-391.
[11]Dar QA,Schott EM,Catheline SE,et al.Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and antiinflammatory in murine posttraumatic osteoarthritis[J].PLo S One,2017,12(4):e0174705.doi:10.1371/journal.pone.0174705.
[12]van den Bosch MH,Blom AB,Kram V,et al.WISP1/CCN4aggravates cartilage degeneration in experimental osteoarthritis[J].Osteoarthritis Cartilage,2017,25(11):1900-1911.doi:10.1016/j.joca.2017.07.012.
[13]Nakamura A,Rampersaud YR,Nakamura S,et al.Micro RNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints[J].Ann Rheum Dis,2019,78(11):111-121.doi:10.1136/annrheumdis-2018-213629.
[14]Abbasi J.Can exercise prevent knee osteoarthritis?[J].JAMA,2017,318(22):2169-2171.doi:10.1001/jama.2017.16144.
[15]Hamamura K,Zhang P,Zhao L,et al.Knee loading reduces MMP13 activity in the mouse cartilage[J].BMC Musculoskelet Disord,2013,14:312.doi:10.1186/1471-2474-14-312.
[16]Malfait AM.Osteoarthritis year in review 2015:biology[J].Osteoarthritis Cartilage,2016,24(1):21-26.doi:10.1016/j.joca.2015.09.010.
[17]Chinzei N,Rai MF,Hashimoto S,et al.Evidence for genetic contribution to variation in post-traumatic osteoarthritis in mice[J].Arthritis Rheumatol,2019,71(3):370-381.doi:10.1002/art.40730.
[18]Bechtold TE,Saunders C,Decker RS,et al.Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling[J].Matrix Biol,2016,52/53/54:339-354.doi:10.1016/j.matbio.2016.03.001.