Vezeridis Peter S, Semeins Cornelis M, Chen Qian, Klein-Nulend Jenneke
Department of Oral Cell Biology, Academic Center of Dentistry Amsterdam (ACTA), Universiteit van Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.
Biochem Biophys Res Commun. 2006 Sep 29;348(3):1082-8. doi: 10.1016/j.bbrc.2006.07.146. Epub 2006 Jul 31.
Osteocytes are thought to orchestrate bone remodeling, but it is unclear exactly how osteocytes influence neighboring bone cells. Here, we tested whether osteocytes, osteoblasts, and periosteal fibroblasts subjected to pulsating fluid flow (PFF) produce soluble factors that modulate the proliferation and differentiation of cultured osteoblasts and periosteal fibroblasts. We found that osteocyte PFF conditioned medium (CM) inhibited bone cell proliferation, and osteocytes produced the strongest inhibition of proliferation compared to osteoblasts and periosteal fibroblasts. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the inhibitory effects of osteocyte PFF CM, suggesting that a change in NO release is at least partially responsible for the inhibitory effects of osteocyte PFF CM. Furthermore, osteocyte PFF CM stimulated osteoblast differentiation measured as increased alkaline phosphatase activity, and l-NAME decreased the stimulatory effects of osteocyte PFF CM on osteoblast differentiation. We conclude that osteocytes subjected to PFF inhibit proliferation but stimulate differentiation of osteoblasts in vitro via soluble factors and that the release of these soluble factors was at least partially dependent on the activation of a NO pathway in osteocytes in response to PFF. Thus, the osteocyte appears to be more responsive to PFF than the osteoblast or periosteal fibroblast with respect to the production of soluble signaling molecules affecting osteoblast proliferation and differentiation.
骨细胞被认为在协调骨重塑过程中发挥作用，但目前尚不清楚骨细胞究竟是如何影响邻近的骨细胞的。在此，我们测试了经受脉动流体流动（PFF）的骨细胞、成骨细胞和骨膜成纤维细胞是否会产生可调节培养的成骨细胞和骨膜成纤维细胞增殖与分化的可溶性因子。我们发现骨细胞PFF条件培养基（CM）抑制骨细胞增殖，并且与成骨细胞和骨膜成纤维细胞相比，骨细胞产生的增殖抑制作用最强。一氧化氮（NO）合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）减弱了骨细胞PFF CM的抑制作用，这表明NO释放的变化至少部分是骨细胞PFF CM抑制作用的原因。此外，骨细胞PFF CM刺激成骨细胞分化，表现为碱性磷酸酶活性增加，而L-NAME降低了骨细胞PFF CM对成骨细胞分化的刺激作用。我们得出结论，经受PFF的骨细胞通过可溶性因子在体外抑制成骨细胞增殖但刺激其分化，并且这些可溶性因子的释放至少部分依赖于骨细胞中NO途径响应PFF的激活。因此，就影响成骨细胞增殖和分化的可溶性信号分子的产生而言，骨细胞似乎比成骨细胞或骨膜成纤维细胞对PFF更敏感。
