Adrenomedullin - a regulator of bone formation
Adrenomedullin - a regulator of bone formation
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DOI：
10.1016/s0167-0115(03)00025-9
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发表时间：
2003-04-15
影响因子：
--
通讯作者：
Reid, IR
中科院分区：
文献类型：
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作者：
Cornish, J;Naot, D;Reid, IR
骨的生长和维持是高度调节的过程。在整个生命过程中，骨不断经历重塑，维持成骨细胞的骨形成和破骨细胞的骨吸收之间的平衡。这种平衡取决于骨微环境中许多全身激素和局部作用因子的协调活动。了解这些因素的作用机制，提供了一个更好的欣赏的细胞和分子基础的骨remodeling.Adrenomedullin最近已被发现刺激成骨细胞在体外增殖，并增加指数的骨形成时，无论是局部或全身给药在体内。肾上腺髓质素受体以及肾上腺髓质素本身在原代成骨细胞和成骨细胞样细胞系中表达。在本文中，我们讨论了肾上腺髓质素在骨中的合成代谢作用，并提出了新的证据肾上腺髓质素在软骨细胞的调节可能发挥的作用。我们发现，肾上腺髓质素刺激增殖的主要软骨细胞在文化和肾上腺髓质素和肾上腺髓质素受体的mRNA表达在这些cells.Studies的结构-活性关系表明，adrenomedullin的成骨作用可以保留在肽片段的分子，缺乏母体分子的血管舒张特性。因此，这些小肽或其类似物是骨质疏松症的合成代谢疗法的有吸引力的候选者。(C)2003 Elsevier Science B.V保留所有权利。
Bone growth and maintenance are highly regulated processes. Throughout life, bone constantly undergoes remodelling, maintaining a balance between bone formation by osteoblasts and bone resorption by osteoclasts. This balance depends on the coordinated activities of many systemic hormones and locally acting factors in the bone microenvironment. Understanding the mechanisms of action of these factors provides a better appreciation of the cellular and molecular basis of bone remodelling.Adrenomedullin has recently been found to stimulate the proliferation of osteoblasts in vitro, and to increase indices of bone formation when administered either locally or systemically in vivo. Adrenomedullin receptors, as well as adrenomedullin itself, are expressed in primary osteoblasts and in osteoblast-like cell lines. In this paper we discuss the anabolic effect of adrenomedullin in bone, and present new evidence for a possible role of adrenomedullin in the regulation of cartilage cells. We show that adrenomedullin stimulates proliferation of primary chondrocytes in culture and that mRNA for adrenomedullin and for adrenomedullin receptors are expressed in these cells.Studies of structure-activity relationships have demonstrated that osteotropic effects of adrenomedullin can be retained in peptide fragments of the molecule which lack the parent molecule's vasodilatory properties. Thus, these small peptides, or their analogues, are attractive candidates as anabolic therapies for osteoporosis. (C) 2003 Elsevier Science B.V All rights reserved.