Aspartic acid racemization reveals a high turnover state in knee compared with hip osteoarthritic cartilage.

Aspartic acid racemization reveals a high turnover state in knee compared with hip osteoarthritic cartilage.
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DOI:
10.1016/j.joca.2015.09.003
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发表时间:
2016-02
影响因子:
7
通讯作者:
Kraus VB
Kraus VB
中科院分区:
医学2区
文献类型:
--
作者:
Catterall JB;Zura RD;Bolognesi MP;Kraus VB

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我们研究了健康软骨和骨关节炎软骨的组织更新。我们挑战长期持有的观点,即骨关节炎(OA)是由所有关节相似的转换过程主导的,并提供证据表明髋关节和膝关节软骨对OA的反应非常不同。对关节置换术时获得的全软骨、胶原和非胶原成分进行D-和l -天冬氨酸(Asp)的定量分析。我们计算了每个组分的Asp外消旋比(Asp- rr =D/D+L Asp),反映了总蛋白的老蛋白比例。与髋关节骨性关节炎相比,膝关节骨性关节炎胶原原纤维(P<0.0001)、胶原蛋白(P =0.007)和非胶原蛋白(P =0.0003)的年龄调整平均asp - rr显著降低,与膝关节骨性关节炎中蛋白合成升高一致。膝关节OA胶原的平均羟脯氨酸/脯氨酸(H/P)比为1.2,与III型胶原的存在一致,而髋关节OA胶原的平均H/P比为0.99,与II型胶原的存在一致。基于Asp-RR,膝关节和髋部OA患者的相对年龄差异有统计学意义(p<0.0005);据估计,患OA的膝关节比非OA患者平均“年轻”30岁,患OA的髋关节比非OA患者“老”10岁。不同关节部位对OA的代谢反应有显著差异。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。这些结果挑战了长期持有的观点,即OA软骨只能进行最小程度的修复,胶原蛋白的损失是不可逆转的。
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 30yrs ‘younger’, and OA hips 10yrs ‘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.