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Subchondral bone and ligament changes precede cartilage degradation in guinea pig osteoarthritis

机译:豚鼠骨关节炎的软骨降解之前软骨下骨和韧带的变化

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There is increasing recognition that osteoarthritis (OA) is a complex disease involving the whole synovial joint, rather than the articular cartilage alone, however its aetiology and pathogenesis is not understood. Our initial studies revealed elevated turnover of bone and ligament collagen in human and mouse OA, respectively. To investigate the relative appearance of pathology in cartilage, bone and ligament, we studied the progression of spontaneous OA in the Dunkin-Hartley (DH) guinea pig knee, and compared with age-matched control Bristol Strain 2 (BS2) knees. The classical radiographic OA score of the DH knees compared to BS2 knees was 2-fold higher at 24 weeks of age. The patella perimeter and subchondral bone density was significantly greater in the DHs at 24 and 36 weeks compared to BS2. The femoral intercondylar notch width was found to be significantly lower in the DHs at 24 and 36 weeks, compared to BS2, indicating bone remodelling at the cruciate ligament (CL) insertion site. We found significantly greater laxity of the DH anterior CL at 12, 16 and 20 weeks compared to BS2. This elevated laxity was associated with increased remodelling of the CLs, based on markers of collagen turnover, and occurred prior to bone and cartilage pathology. We propose that the laxity of the CL leads to remodelling of the subchondral bone, and intercondylar notch, due to a change in load through the joint. Remodelling of the CLs and bone occurs prior to and concomitant with histopathological changes in the articular cartilage respectively, demonstrating the fundamental role of the ligament and subchondral bone in the aetiology of knee OA.
机译:人们越来越认识到,骨关节炎(OA)是一种复杂的疾病,涉及整个滑膜关节,而不是单纯的关节软骨,但是其病因和发病机理尚不清楚。我们的初步研究表明,人和小鼠OA中骨骼和韧带胶原蛋白的周转率分别升高。为了研究软骨,骨骼和韧带中病理学的相对表现,我们研究了Dunkin-Hartley(DH)豚鼠膝关节自发性OA的进展,并与年龄匹配的对照组Bristol Strain 2(BS2)膝盖进行了比较。与BS2膝相比,DH膝的经典放射学OA评分在24周龄时高2倍。与BS2相比,DH在第24和36周时weeks骨周长和软骨下骨密度显着更高。与BS2相比,在第24周和第36周时,DHs的股骨con间切口宽度显着降低,表明在十字韧带(CL)插入位点的骨重塑。我们发现,与BS2相比,DH前CL在第12、16和20周的松弛度明显更大。基于胶原蛋白更新的标记,这种松弛度升高与CL的重塑增加有关,并且发生在骨骼和软骨病理之前。我们建议,由于通过关节负荷的变化,CL的松弛会导致软骨下骨的重建和con间凹口。 CLs和骨骼的重塑分别发生在关节软骨的组织病理学改变之前和同时,证明了韧带和软骨下骨在膝骨关节炎的病因学中的基本作用。

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