Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway
Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway
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DOI：
10.1016/j.yexcr.2005.05.021
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发表时间：
2005-09-10
影响因子：
3.7
通讯作者：
Liao, EY
中科院分区：
文献类型：
--
作者：
Luo, XH;Guo, LJ;Liao, EY
脂肪细胞可以高效、特异地表达脂联素，在成骨细胞中已检测到脂联素受体(AdipoR1)。本研究旨在探讨脂联素在成骨细胞增殖和分化中的作用。在人成骨细胞中检测到AdipoRI蛋白。脂联素促进成骨细胞增殖，使碱性磷酸酶(ALP)活性、骨钙素和I型胶原产量呈剂量和时间依赖性增加，矿化基质增多。小干扰RNA(SiRNA)抑制AdipoRl可抑制脂联素诱导的细胞增殖和碱性磷酸酶的表达。脂联素可诱导成骨细胞p38丝裂原活化蛋白激酶(MAPK)和c-jun氨基末端激酶(JNK)的激活，但不能激活ERK1/2，这些作用可被siRNA抑制AdipoR1所阻断。此外，用JNK抑制剂SP600125预处理成骨细胞可阻断脂联素诱导的细胞增殖。P38抑制剂SB203580阻断脂联素诱导的人成骨细胞碱性磷酸酶的活性，提示脂联素可诱导人成骨细胞增殖分化，其增殖反应通过AdipoR/JNK途径实现，而分化反应则通过AdipoR/p38途径实现。这些发现表明，成骨细胞是脂联素的直接靶点。(C)2005 Elsevier Inc.保留所有权利。
Adipocytes can highly and specifically express adiponectin, and the adiponectin receptor (AdipoR1) has been detected in bone-forming cells. The present study was undertaken to investigate the action of adiponectin on osteoblast proliferation and differentiation. AdipoRI protein was detected in human osteoblasts. Adiponectin promoted osteoblast proliferation and resulted in a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production, and an increase in mineralized matrix. Suppression of AdipoRl with small-interfering RNA (siRNA) abolished the adiponectin-induced cell proliferation and ALP expression. Adiponectin induces activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2 in osteoblasts, and these effects were blocked by suppression of AdipoR1 with siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125 abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580 blocked the adiponectin-induced ALP activity.These data indicate that adiponectin induces human osteoblast proliferation and differentiation, and the proliferation response is mediated by the AdipoR/JNK pathway, while the differentiation response is mediated via the AdipoR/p38 pathway. These findings suggest that osteoblasts are the direct targets of adiponectin. (c) 2005 Elsevier Inc. All rights reserved.