The role of chondrocyte senescence in osteoarthritis
The role of chondrocyte senescence in osteoarthritis
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DOI：
10.1046/j.1474-9728.2002.00008.x
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发表时间：
2002-10-01
期刊：
影响因子：
7.8
通讯作者：
Clark, IM
中科院分区：
文献类型：
--
作者：
Price, JS;Waters, JG;Clark, IM
当正常体细胞停止分裂时，就会发生复制性衰老。衰老细胞仍然存活，但表现出表型改变，例如基质金属蛋白酶（MMPs）的表达改变；这些酶被认为与软骨破坏有关。假设细胞在衰老过程中耗尽了它们的复制潜力，年龄是骨关节炎（OA）的主要危险因素。因此，我们假设衰老或病变软骨中的软骨细胞衰老并伴有相关的表型变化，从而促进OA的发生或进展。关节软骨来自于接受关节置换术的OA患者，“正常”软骨来自于髋部骨折的创伤手术。使用衰老相关的β -半乳糖苷酶（sa - β -gal）标记来鉴定衰老细胞。端粒长度采用Southern blot测定。采用Taqman(R) RT-PCR检测mRNA水平上MMP的表达。无论患者年龄如何，对照软骨均未观察到sa - β -gal染色。与此相反，在病变附近受损的CIA软骨中观察到SA-P-gal染色。从病变附近部位分离的培养软骨细胞比从远端部位或正常软骨分离的培养细胞含有更高百分比的sa - β -gal阳性细胞。同一关节中病灶附近细胞的端粒平均长度比远端细胞短；因此，前种群经历了细胞分裂。骨性关节炎软骨中胶原酶MMP-1、-8和-13以及金属蛋白酶组织抑制剂(TIMP)-1的表达发生改变，但在同一关节的病变部位和远端部位之间没有差异（即衰老细胞与蛋白酶/抑制剂表达之间没有相关性）。
Replicative senescence occurs when normal somatic cells stop dividing. Senescent cells remain viable, but show alterations in phenotype, e.g. altered expression of matrix metalloproteinases (MMPs); these enzymes are known to be involved in cartilage destruction. It is assumed that cells deplete their replicative potential during aging, and age is a major risk factor for osteoarthritis (OA). Therefore, we hypothesized that chondrocytes in aging or diseased cartilage become senescent with associated phenotypic changes contributing to development or progression of OA.Articular cartilage was obtained from OA patients undergoing arthroplasty, with 'normal' cartilage from trauma surgery for hip fracture. Senescent cells were identified using the senescence-associated beta-galactosidase (SA-beta-gal) marker. Telomere length was assessed using Southern blot. MMP expression was measured at the mRNA level using Taqman(R) RT-PCR.No SA-beta-gal staining was observed in control cartilage regardless of patient age. In contrast, SA-P-gal staining was observed in damaged CIA cartilage adjacent to the lesion. Cultured chondrocytes isolated from sites near a lesion contained a greater percentage of SA-beta-gal positive cells than cultures isolated from distal sites or normal cartilage. Mean telomere length was shorter in cells near the lesion compared to distal sites in the same joint; thus the former population has undergone cell division. The expression of collagenases MMP-1, -8 and -13 and tissue inhibitor of metalloproteinases (TIMP)-1 was altered in OA cartilage, but no difference was detected between lesion and distal sites in the same joint (i.e. no correlation was found between senescent cells and proteinase/inhibitor expression).