Catterall J B, Zura R D, Bolognesi M P, Kraus V B
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Osteoarthritis Cartilage. 2016 Feb;24(2):374-81. doi: 10.1016/j.joca.2015.09.003. Epub 2015 Sep 28.
We investigated tissue turnover in healthy and osteoarthritic cartilage. We challenge long held views that osteoarthritis (OA) is dominated by a similar turnover process in all joints and present evidence that hip and knee cartilage respond very differently to OA.
d- and l-Aspartate (Asp) were quantified for whole cartilage, collagen and non-collagenous components of cartilage obtained at the time of joint replacement. We computed the Asp racemization ratio (Asp-RR = d/d + l Asp), reflecting the proportion of old to total protein, for each component.
Compared with hip OA, knee OA collagen fibrils (P < 0.0001), collagen (P = 0.007), and non-collagenous proteins (P = 0.0003) had significantly lower age-adjusted mean Asp-RRs consistent with elevated protein synthesis in knee OA. Knee OA collagen had a mean hydroxyproline/proline (H/P) ratio of 1.2 consistent with the presence of type III collagen whereas hip OA collagen had a mean H/P ratio of 0.99 consistent with type II collagen. Based on Asp-RR, the relative age was significantly different in knee and hip OA (P < 0.0005); on average OA knees were estimated to be 30 yrs 'younger', and OA hips 10 yrs 'older' than non-OA.
The metabolic response to OA was strikingly different by joint site. Knee OA cartilage evinced an anabolic response that appeared to be absent in hip OA cartilage. These results challenge the long held view that OA cartilage is capable of only minimal repair and that collagen loss is irreversible.
我们研究了健康软骨和骨关节炎软骨的组织更新情况。我们对长期以来认为骨关节炎(OA)在所有关节中都由相似的更新过程主导这一观点提出质疑,并提供证据表明髋关节和膝关节软骨对OA的反应截然不同。
对关节置换时获取的整个软骨、软骨的胶原蛋白和非胶原蛋白成分中的d-天冬氨酸(Asp)和l-天冬氨酸进行定量分析。我们计算了每个成分的天冬氨酸消旋化率(Asp-RR = d/d + l Asp),该比率反映了旧蛋白与总蛋白的比例。
与髋关节OA相比,膝关节OA的胶原纤维(P < 0.0001)、胶原蛋白(P = 0.007)和非胶原蛋白(P = 0.0003)的年龄校正平均Asp-RR显著更低,这与膝关节OA中蛋白质合成增加一致。膝关节OA胶原蛋白的平均羟脯氨酸/脯氨酸(H/P)比率为1.2,与III型胶原蛋白的存在一致,而髋关节OA胶原蛋白的平均H/P比率为0.99,与II型胶原蛋白一致。基于Asp-RR,膝关节和髋关节OA的相对年龄有显著差异(P < 0.0005);平均而言,OA膝关节估计比非OA膝关节“年轻”30岁,OA髋关节比非OA髋关节“老”10岁。
不同关节部位对OA的代谢反应明显不同。膝关节OA软骨表现出合成代谢反应,而髋关节OA软骨似乎没有这种反应。这些结果对长期以来认为OA软骨仅能进行最小程度修复且胶原蛋白损失不可逆的观点提出了挑战。