FAK inhibition protects condylar cartilage under excessive mechanical stress
FAK inhibition protects condylar cartilage under excessive mechanical stress
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FAK 抑制可在过度机械应力下保护髁软骨
DOI：
10.1111/odi.13494
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发表时间：
2020
期刊：
影响因子：
3.8
通讯作者：
Tanimoto K
中科院分区：
文献类型：
--
作者：
Yanoshita M.;Hirose N.;Sumi C.;Takano M.;Nishiyama S.;Tsuboi E.;Onishi A.;Yamauchi Y.;Asakawa Y.;Kunimatsu R.;Tanimoto K
过度的机械应力被认为是颞下颌关节（TMJ）骨关节炎（OA）的主要原因。粘着斑激酶（FAK）是一种细胞质非受体酪氨酸激酶，参与多种信号传导途径。关于FAK在TMJ-OA中的功能报道很少。在本研究中，我们研究了FAK抑制TMJ软骨过度机械负荷stress.Materials和MethodsArticular软骨外植体收获从大鼠TMJ和机械负荷中存在的FAK抑制剂在器官培养的影响。应用机械负荷加或不加FAK抑制剂后，检测炎性细胞因子的基因表达。采用苏木精-伊红、番红O、坚牢绿色、甲苯胺蓝、TUNEL染色及免疫组化等方法检测关节软骨组织中IL-1β和MMP-13的表达。FAK抑制剂治疗还抑制了肥大区IL-1β和MMP-13的蛋白表达，如免疫组织学所确定的。
ObjectivesExcessive mechanical stress is assumed to be a major cause of temporomandibular joint (TMJ) osteoarthritis (OA). +Focal adhesion kinase (FAK) is a cytoplasmic non‐receptor tyrosine kinase involved in a variety of signaling pathways. Little has been reported on the function of FAK in TMJ‐OA. In the present study, we investigated the effect of FAK inhibition on TMJ cartilage under excessive mechanical loading stress.Materials and MethodsArticular cartilage explants were harvested from the TMJ of rats and subjected to mechanical loading in the presence of an FAK inhibitor in organ culture. The gene expression of inflammatory cytokines was examined after the application of mechanical loading with or without FAK inhibitor. Paraffin‐embedded sections of articular cartilage were stained with hematoxylin and eosin, safranin O and fast Green, toluidine blue, TUNEL staining, and immunohistochemical staining and was performed to investigate the protein expression of IL‐1β and MMP‐13.ResultsTreatment with FAK inhibitor reduced the gene expression of inflammatory cytokines and inhibited the degradation of articular cartilage, as determined histologically. FAK inhibitor treatment also suppressed the protein expression of IL‐1β and MMP‐13 in the hypertrophic zone, as determined immunohistologically.ConclusionTreatment with FAK inhibitor suppresses inflammation and protects condylar cartilage under excessive mechanical loading.