Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts
Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts
复制标题
破骨细胞生成受到成骨细胞产生的 D-丝氨酸的负调节
DOI：
10.1002/jcp.24048
复制
发表时间：
2012
期刊：
影响因子：
5.6
通讯作者：
Yukio Yoneda
中科院分区：
文献类型：
--
作者：
Takeshi Takarada;Mika Takarada-Iemata;Yoshifumi Takahata;Daisuke Yamada;Tomomi Yamamoto;Yukari Nakamura;Eiichi Hinoi;Yukio Yoneda
我们已经证明了丝氨酸消旋酶(SR)在软骨细胞中的功能表达，该酶负责从软骨中的丝氨酸合成D-丝氨酸(Ser)。在这项研究中，我们评估了SR在成骨细胞和骨吸收破骨细胞中可能的功能表达。新生大鼠胫骨切片中的成骨细胞和体外释放丝氨酸的培养大鼠颅骨成骨细胞中均有SR基因的表达，而从小鼠骨髓前体细胞分化而来的破骨细胞中未见SR基因的表达。Tod-Ser对成骨细胞碱性磷酸酶活性和钙离子积累无明显影响，但在浓度为0.10~1 mM范围内呈浓度依赖性地抑制成骨细胞的分化和成熟，不影响破骨细胞的存活。相反，L-丝氨酸促进破骨细胞分化，且对抑制作用敏感。成熟的破骨细胞表达氨基酸转运蛋白B0，+(ATB0，+)和丙氨酸、丝氨酸和半胱氨酸氨基酸转运蛋白-2(ASCT2)的mRNA，它们分别能够类似地结合细胞外的L-和d-Ser。通过siRNA敲除这些转运体，可以阻止BYL-Ser促进破骨细胞分化和BYD-Ser抑制破骨细胞分化。这些结果表明，D-丝氨酸可能通过ATB0、+和ASCT2共同介导的丝氨酸对映体在破骨细胞合成并随后从相邻成骨细胞释放后在破骨细胞中发挥关键作用。J.细胞。物理。227：3477-3487,2012。©2012 Wiley期刊，Inc.
We have shown the functional expression by chondrocytes of serine racemase (SR) which is responsible for the synthesis ofD‐serine (Ser) fromL‐Ser in cartilage. In this study, we evaluated the possible functional expression of SR by bone‐forming osteoblasts and bone‐resorbing osteoclasts. Expression of SR mRNA was seen in osteoblasts localized at the cancellous bone surface in neonatal rat tibial sections and in cultured rat calvarial osteoblasts endowed to releaseD‐Ser into extracellular medium, but not in cultured osteoclasts differentiated from murine bone marrow progenitor cells. Sustained exposure toD‐Ser failed to significantly affect alkaline phosphatase activity and Ca2+accumulation in cultured osteoblasts, but significantly inhibited differentiation and maturation in a concentration‐dependent manner at a concentration range of 0.1–1 mM without affecting cellular survival in cultured osteoclasts. By contrast,L‐Ser promoted osteoclastic differentiation in a manner sensitive to the inhibition byD‐Ser. Matured osteoclasts expressed mRNA for the amino acid transporter B0,+(ATB0,+) and the system alanine, serine, and cysteine amino acid transporter‐2 (ASCT2), which are individually capable of similarly incorporating extracellularL‐ andD‐Ser. Knockdown of these transporters by siRNA prevented both the promotion byL‐Ser and the inhibition byD‐Ser of osteoclastic differentiation in pre‐osteoclastic RAW264.7 cells. These results suggest thatD‐Ser may play a pivotal role in osteoclastogenesis through a mechanism related to the incorporation mediated by both ATB0,+and ASCT2 of serine enantiomers in osteoclasts after the synthesis and subsequent release from adjacent osteoblasts. J. Cell. Physiol. 227: 3477–3487, 2012. © 2012 Wiley Periodicals, Inc.