Cell-to-cell adhesion via intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 pathway is involved in 1α,25(OH)2D3, PTH and IL-1α-induced osteoclast differentiation and bone resorption
Cell-to-cell adhesion via intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 pathway is involved in 1α,25(OH)2D3, PTH and IL-1α-induced osteoclast differentiation and bone resorption
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DOI：
10.1507/endocrj.49.483
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发表时间：
2002-08-01
影响因子：
2
通讯作者：
Tanaka, Y
中科院分区：
文献类型：
--
作者：
Okada, Y;Morimoto, I;Tanaka, Y
破骨细胞前体的分化和破骨细胞的功能都需要细胞间的相互作用。本研究旨在探讨1，25-二羟基维生素D-3(1，25D)、甲状旁腺素(PTH)、白介素1α(IL-1α)和前列腺素E(PGE)(2)在破骨细胞形成和骨吸收过程中是否通过细胞间黏附分子(ICAM)-1/白细胞功能相关抗原(LFA)-1途径依赖于细胞间相互作用。我们发现小鼠成骨细胞表达ICAM-1，PTH、IL-1α或1，25D可促进其表达，但PGE(2)对其表达无明显影响。在骨吸收实验中，抗ICAM-1单抗和/或抗LFA-1单抗均可抑制1，25D-、PTH和IL-1α刺激的骨吸收，而基础和前列腺素E(2)刺激的骨吸收不受这些单抗的影响。此外，在小鼠骨髓培养体系中，加入抗ICAM-1单抗和/或抗LFA-1单抗可抑制1，25D(10 NM)、PTH(10 ng/ml)或IL-1α(10 ng/ml)对破骨细胞样细胞(OCL)的刺激作用。在小鼠脾细胞和成骨细胞共培养体系中，ICAM-1/LFA-1的相互作用也参与了1，25D、PTH和IL-1α刺激的TRAP阳性单核细胞的形成。然而，抗ICAM-1单抗和抗LFA-1单抗并不改变1，25D或PTH刺激的骨髓培养中核因子-kappaB受体激活剂(RANKL)的mRNA转录。综上所述，我们认为ICAM-1介导的成骨细胞和破骨细胞前体的细胞间黏附参与了1，25D、PTH和IL-1α刺激的RANKL依赖的破骨细胞成熟。
Cell-to-cell interaction is required for the differentiation of osteoclast precursors as well as for osteoclast function. The present study was undertaken to determine whether 1,25 dihydroxyvitamin D-3 (1,25D), PTH, IL-1alpha and PGE(2) depend on cell-to-cell interactions through the intercellular adhesion molecule (ICAM)-1/leukocyte function-associated antigen (LFA)-1 pathway in osteoclast formation and bone resorption. We found that mouse osteoblasts expressed ICAM-1 and that the expression was increased by treatment with PTH, IL-1alpha or 1,25D, but not by PGE(2). In resorption assays measuring either Ca-45 release from bone organ cultures or pit formation in bone cell cultures, 1,25D-, PTH- and IL-1alpha-stimulated resorption was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and/or anti-LFA-1 mAb, while basal and PGE(2)-Stimulated bone resorbing activities were not affected by these mAbs. Furthermore, in a mouse bone marrow culture system, stimulation of osteoclast-like (OCL) cell formation by 1,25D (10 nM), PTH (10 ng/ml) or IL-1alpha (10 ng/ml) was inhibited by the addition of anti-ICAM-1 mAb and/or anti-LFA-1 mAb. In a coculture system of murine spleen cells and osteoblasts, the ICAM-1/LFA-1 interaction was also involved in 1,25D-, PTH- and IL-1alpha-stimulated TRAP-positive MNC formation. However, anti-ICAM-1 mAb and anti-LFA-1 mAb did not alter either 1,25D- or PTH-stimulated receptor activator of NF-kappaB ligand (RANKL) mRNA transcription in bone marrow cultures. Taken together, we here propose that ICAM-1-mediated cell-to-cell adhesion of osteoblasts and osteoclast precursors is involved in RANKL-dependent osteoclast maturation stimulated by 1,25D, PTH, and IL-1alpha.