整合素是介导多种生物学功能的异源二聚体跨膜受体，在骨关节炎（OA）的发病机制中起关键作用。这可能为OA治疗的发展提供新的靶点。然而,整合素在OA不同阶段的作用尚不清楚。
本研究旨在综合所有已发表的关于整合素受体在OA不同阶段的作用的临床前证据，以确定药物开发在缓解OA发病机制中的潜在靶标。
主要的电子数据库用于识别相关的原始文章。使用SYRCLE偏倚风险工具评估所有纳入研究的方法学质量。我们使用带有随机效应的通用逆方差模型来计算标准化平均差（SMD）和95％置信区间（CI）。
本系统综述包括17项研究。整合素α5β1的激活增加组织病理学评分在早期[SMD，6.39；95CI(2.90，9.87)；p=0.0003]和后期[SMD，3.41；95CI（2.44，4.38）；p<0.00001]OA阶段。整合素α5β1也增加了核心分解代谢因子，如MMP-3，IL-1β，和TNF-α。有趣的是,α5β1整合素的失活并没有改变组织病理学评分(p=0.84).同样，β1整合素在OA的两个阶段都显着增加了组织病理学评分[早期；SMD，7.13；95CI（2.01，12.24）；p=0.006]；[晚；SMD，10.25；95CI（5.11，15.39）；p<0.0001]，并增加MMP-13水平。然而,整合素β1在OA早期上调，晚期下调。此外，α2β1整合素显著增加组织病理学评分[SMD，3.14；95CI(2.18，4.10)；p<0.00001]和MMP-13[SMD，2.24；95CI（0.07，4.41）；p=0.04]。去激活整合素α1β1增加晚期组织病理学评分[SMD，1.53；95CI（0.80，2.26）；p<0.0001]，但不是在早期[SMD，0.90；95CI（-1.65，3.45）；p=0.49]期OA。
这项研究提供了证据，证明α5β1、α2β1和α1β1整合素可能是未来药物开发缓解OA发病机制的潜在靶点。需要进一步的工作来通过在OA的不同阶段激活/失活这些受体来建立我们的发现。
Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive.
This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis.
Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI).
Seventeen studies were included in this systematic
review. Integrin α5β1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p < 0.00001] stage of OA. Integrin α5β1 also increased the core catabolic factors like MMP-3, IL-1β, and TNF-α. Interestingly, the inactivation of α5β1 integrin did not change the histopathological score (p = 0.84). Similarly, β1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p < 0.0001], and increased the MMP-13 levels. However, integrin β1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2β1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p < 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1β1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p < 0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p = 0.49] stage of OA.
This study provides evidence that α5β1, α2β1, and α1β1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.
