αB-crystallin (CRYAB) regulates the proliferation, apoptosis, synthesis and degradation of extracellular matrix of chondrocytes in osteoarthritis
αB-crystallin (CRYAB) regulates the proliferation, apoptosis, synthesis and degradation of extracellular matrix of chondrocytes in osteoarthritis
复制标题
α B-晶状体蛋白 (CRYAB) 调节骨关节炎中软骨细胞的增殖、凋亡、合成和降解
DOI：
10.1016/j.yexcr.2019.06.004
复制
发表时间：
2019-09-15
影响因子：
3.7
通讯作者：
Ma, Changyan
中科院分区：
文献类型：
--
作者：
Bao, Qianyi;Yang, Dawei;Ma, Changyan
骨关节炎（OA）是一种慢性关节疾病，目前尚难治愈.α B-晶体蛋白（α B-crystallin，α B-crystallin AB）已被鉴定为OA软骨中的下调基因。然而，确切的作用和潜在的分子机制，在OA的进展中的EPOAB尚未阐明。在本研究中，我们发现OA患者的软骨中的CITAAB的表达显著低于无OA病史的患者的软骨。我们通过内侧半月板失稳（destabilization of the medial meniscus，DMM）手术建立了OA小鼠模型，发现OA软骨中的CD 4AB表达也低于正常软骨。此外，我们证明了在软骨形成分化和软骨发育过程中，CDMAAB的表达增加。功能分析显示，过表达的CCLAB促进软骨细胞的增殖和抑制凋亡，而敲低的CCLAB呈现相反的结果。此外，过表达的CCLAB上调的合成代谢标志物，Col 2a 1和ACAN的表达，并减少了分解代谢标志物，MMP 13和ADAMTS 5的表达。相反，敲低BABAB阻断了合成代谢标志物的表达，并增加了分解代谢标志物的表达。以上结果表明，CCL-AB促进软骨细胞增殖和细胞外基质生成，同时抑制软骨细胞凋亡和软骨降解。因此，CRAAB可能是OA治疗的潜在治疗靶点。
Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Alpha B-crystallin (CRYAB) has been identified as a downregulated gene in OA cartilage. However, the precise roles and underlying molecular mechanisms of CRYAB in OA progression have not been elucidated. In the present study, we found that the expression of CRYAB in cartilages from patients with OA was significantly lower than that in the cartilages from patients with no prior medical history of OA. We established mouse models with OA by destabilization of the medial meniscus (DMM) surgery and found that the expression of CRYAB in OA cartilage was lower than that in the normal cartilages, too. Moreover, we demonstrated that the expression of CRYAB was increased during chondrogenic differentiation and cartilage development. Functional assays revealed that overexpression of CRYAB promoted the proliferation of chondrocytes and inhibited apoptosis, while knockdown of CRYAB presented opposite results. In addition, overexpression of CRYAB upregulated the expression of anabolic markers, Col2a1 and ACAN, and reduced the expression of catabolic markers, MMP13 and ADAMTS5. Conversely, knockdown of CRYAB blocked the expression of the anabolic markers and increased the expression of catabolic markers. Collectively, the results suggest that CRYAB promoted the proliferation and extracellular matrix production of chondrocytes, and inhibited chondrocytes apoptosis and cartilage degradation simultaneously. Thus, CRYAB might be a potential therapeutic target for OA treatment.