Osteoblast programmed cell death (apoptosis): Modulation by growth factors and cytokines
Osteoblast programmed cell death (apoptosis): Modulation by growth factors and cytokines
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DOI：
10.1359/jbmr.1998.13.5.793
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发表时间：
1998-05-01
影响因子：
6.2
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
一旦成骨细胞完成了它们的骨形成功能，它们要么被捕获在骨基质中并成为骨细胞，要么作为衬里细胞留在表面上。尽管如此，在计数衬里细胞和骨细胞后，最初存在于重塑部位的50-70%的成骨细胞不能被解释。我们假设缺失的成骨细胞死于细胞凋亡，并且骨微环境中产生的生长因子和细胞因子影响这一过程。我们报道了小鼠成骨细胞MC 3 T3-E1在去除血清或加入肿瘤坏死因子（TNF）后发生凋亡，如末端脱氧核苷酸转移酶介导的dUTP-缺口末端标记和DNA片段化研究所示。转化生长因子-β和白细胞介素-6（IL-6）型细胞因子具有抗凋亡作用，因为它们能够抵消血清饥饿或TNF的作用，另外，抗Pas抗体刺激人成骨细胞MG-63细胞凋亡，IL-6类细胞因子阻止了这种变化。MG-63细胞凋亡的诱导与促凋亡蛋白bar与抗凋亡蛋白bcl-2比值的增加有关，制瘤素M阻止了这种变化。对小鼠松质骨未脱钙切片的检查显示存在凋亡细胞，通过它们靠近类骨质缝以及与立方成骨细胞并置来识别为成骨细胞，假设成骨细胞的寿命为300小时，细胞凋亡的发生率为0.6%，我们计算出体内经历这一过程的部分确实可以解释缺失的成骨细胞，这些发现证实成骨细胞经历凋亡，并强烈表明该过程可以通过骨微环境中产生的生长因子和细胞因子来调节。
Once osteoblasts have completed their bone-forming function, they are either entrapped in bone matrix and become osteocytes or remain on the surface as lining cells. Nonetheless, 50-70% of the osteoblasts initially present at the remodeling site cannot be accounted for after enumeration of lining cells and osteocytes, We hypothesized that the missing osteoblasts die by apoptosis and that growth factors and cytokines produced in the bone microenvironment influence this process. We report that murine osteoblastic MC3T3-E1 cells underwent apoptosis following removal of serum, or addition of tumor necrosis factor (TNF), as indicated by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and DNA fragmentation studies, Transforming growth factor-beta and interleukin-6 (IL-6)-type cytokines had antiapoptotic effects because they were able to counteract the effect of serum starvation or TNF, In addition, anti-Pas antibody stimulated apoptosis of human osteoblastic MG-63 cells and IL-6-type cytokines prevented these changes, The induction of apoptosis in MG-63 cells was associated with an increase in the ratio of the proapoptotic protein bar to the antiapoptotic protein bcl-2, and oncostatin M prevented this change. Examination of undecalcified sections of murine cancellous bone revealed the presence of apoptotic cells, identified as osteoblasts by their proximity to osteoid seams and their juxtaposition to cuboidal osteoblasts, Assuming an osteoblast life span of 300 h and a prevalence of apoptosis of 0.6%, we calculated that the fraction that undergo this process in vivo can indeed account for the missing osteoblasts, These findings establish that osteoblasts undergo apoptosis and strongly suggest that the process can be modulated by growth factors and cytokines produced in the bone microenvironment.