The Fas/Fas ligand system inhibits differentiation of murine osteoblasts but has a limited role in osteoblast and osteoclast apoptosis.
The Fas/Fas ligand system inhibits differentiation of murine osteoblasts but has a limited role in osteoblast and osteoclast apoptosis.
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DOI：
10.4049/jimmunol.178.6.3379
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发表时间：
2007-03-15
期刊：
影响因子：
--
通讯作者：
Marusić A
中科院分区：
文献类型：
--
作者：
Kovacić N;Lukić IK;Grcević D;Katavić V;Croucher P;Marusić A
通过 Fas/Fas 配体 (FasL) 进行的细胞凋亡是免疫系统稳态的重要调节因子，但其在骨稳态中的作用尚不清楚。我们系统地分析了：a）体外成骨细胞生成和破骨细胞生成过程中Fas/FasL的表达，b）FasL对细胞凋亡和成骨细胞/破骨细胞分化的影响，以及c）Fas或FasL缺陷小鼠的成骨细胞生成和破骨细胞生成。 Fas的表达随着成骨细胞的分化而增加。 FasL 的添加微弱地增加了破骨细胞和成骨细胞培养物中凋亡细胞的比例。在集落形成单位测定中，FasL降低了成骨细胞集落的比例，但不影响集落总数，表明Fas/FasL对成骨细胞分化有特异性抑制作用。该效果取决于 caspase 8 的激活，并且是特异性的，因为在成骨细胞培养物中添加 FasL 会显着降低成骨细胞分化所需的 runt 相关转录因子 2 (Runx2) 的基因表达。没有功能性 Fas 或 FasL 的小鼠的骨髓与野生型小鼠的骨髓具有相似的破骨细胞潜能，但离体产生更多的成骨细胞集落。这些集落的成骨细胞基因 Runx2、骨桥蛋白、碱性磷酸酶、骨唾液蛋白、骨钙素和骨保护素的表达增加。我们的结果表明，Fas/FasL 系统主要通过抑制祖细胞分化而不是诱导细胞凋亡来控制成骨细胞分化。在破骨细胞生成过程中，Fas/FasL 系统对破骨细胞祖细胞凋亡的影响可能有限。该研究表明 Fas/FasL 系统在成骨细胞分化中发挥关键作用，并为免疫系统与骨骼之间的相互作用提供了新的见解。
Apoptosis through Fas/Fas ligand (FasL) is an important regulator of immune system homeostasis but its role in bone homeostasis is elusive. We systematically analyzed: a) the expression of Fas/FasL during osteoblastogenesis and osteoclastogenesis in vitro, b) the effect of FasL on apoptosis and osteoblastic/osteoclastic differentiation, and c) osteoblastogenesis and osteoclastogenesis in mice deficient in Fas or FasL. The expression of Fas increased with osteoblastic differentiation. Addition of FasL weakly increased the proportion of apoptotic cells in both osteoclastogenic and osteoblastogenic cultures. In a colony forming unit assay, FasL decreased the proportion of osteoblast colonies but did not affect the total number of colonies, indicating specific inhibitory effect of Fas/FasL on osteoblastic differentiation. The effect depended on the activation of caspase 8 and was specific, as addition of FasL to osteoblastogenic cultures significantly decreased gene expression for runt-related transcription factor 2 (Runx2) required for osteoblastic differentiation. Bone marrow from mice without functional Fas or FasL had similar osteoclastogenic potential as bone marrow from wild-type mice, but generated more osteoblast colonies ex vivo. These colonies had increased expression of the osteoblast genes Runx2, osteopontin, alkaline phosphatase, bone sialoprotein, osteocalcin, and osteoprotegerin. Our results indicate that Fas/FasL system primarily controls osteoblastic differentiation by inhibiting progenitor differentiation and not by inducing apoptosis. During osteoclastogenesis, Fas/FasL system may have a limited effect on osteoclast progenitor apoptosis. The study suggests that Fas/FasL system plays a key role in osteoblastic differentiation and provides novel insight into the interactions between the immune system and bone.
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影响因子：
--
作者：
Ogawa, Y;Ohtsuki, M;Matsuno, H
通讯作者：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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