Department of Physiology, University of Veterinary Sciences, Brno, Czech Republic.
Physiol Res. 2023 Mar 8;72(1):117-121. doi: 10.33549/physiolres.934945. Epub 2022 Dec 22.
During bone development, FasL acts not only through the traditional apoptotic mechanism regulating the amount of bone-resorbing osteoclasts, but there is also growing evidence about its effect on cell differentiation. Expression of osteoblastic factors was followed in non differentiated and differentiating primary calvarial cells obtained from FasL-deficient (gld) mice. The gld cells showed decreased expression of the key osteoblastic molecules osteocalcin (Ocn), osteopontin (Opn), and alkaline phosphatase (Alpl) in both groups. Notably, receptor activator of nuclear factor kappa-B ligand (Rankl) was unchanged in non-differentiated gld vs. wild type (wt) cells but decreased in differentiating gld cells. Osteoprotegerin (Opg) in the gld samples was increased in both groups. Opg vs. Rankl expression levels favored Opg in the case of non-differentiated cells but Rankl in differentiating ones. These results expand information on the involvement of FasL in non-apoptotic cell pathways related to osteoblastogenesis and consequently also osteoclastogenesis and pathologies such as osteoporosis.
在骨骼发育过程中,FasL 不仅通过调节破骨细胞数量的传统凋亡机制起作用,而且越来越多的证据表明它对细胞分化也有影响。对从小鼠 FasL 缺失(gld)获得的未分化和分化初级颅骨细胞中的成骨细胞因子表达进行了研究。gld 细胞表现出关键成骨分子骨钙素(Ocn)、骨桥蛋白(Opn)和碱性磷酸酶(Alpl)在两组中的表达降低。值得注意的是,核因子 κB 受体激活剂配体(Rankl)在未分化的 gld 与野生型(wt)细胞中的表达没有改变,但在分化的 gld 细胞中降低。gld 样本中的骨保护素(Opg)在两组中均增加。Opg 与 Rankl 的表达水平在未分化细胞中有利于 Opg,但在分化细胞中有利于 Rankl。这些结果扩展了关于 FasL 参与与成骨细胞发生相关的非凋亡细胞途径的信息,从而也参与了破骨细胞发生和骨质疏松症等病理。