Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading
Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading
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DOI：
10.1016/j.bone.2009.01.004
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发表时间：
2009-05-01
期刊：
影响因子：
4.1
通讯作者：
Rauvala, H.
中科院分区：
文献类型：
--
作者：
Imai, S.;Heino, T. J.;Rauvala, H.
HB-GAM（也称为多效生长因子）是一种在骨中高度表达的细胞基质相关蛋白。它影响成骨细胞功能，因此可能在骨发育和重塑中发挥作用。为探讨HB-GAM在体内和体外骨组织中的作用，以HB-GAM缺陷小鼠为研究对象，采用组织学、组织形态计量学、放射学、生物力学和mu-CT等方法，观察制动对HB-GAM缺陷小鼠骨组织的影响。研究了HB-GAM的体内定位。体外培养的MLO-Y 4骨细胞在流体剪切力作用下，通过消减杂交、定量PCR和Western blot检测基因和蛋白的表达。在rhHB-GAM存在下培养人破骨细胞，测定其形成和吸收活性，与以往报道一致，HB-GAM基因敲除小鼠骨骼结构发育正常。然而，在2个月大时观察到承重骨的生长迟缓，这表明与体力活动有关。成年HB-GAM缺陷小鼠的特征在于低骨形成和骨质减少，以及对固定依赖性骨重建的抵抗。HB-GAM在体内定位于骨细胞及其突起周围，体外机械负荷可上调骨细胞HB-GAM的表达。HB-GAM在体外对人破骨细胞的形成和吸收无影响。综上所述，我们的结果表明，HB-GAM是所有的骨细胞源性因子，可以参与介导机械负荷对骨的成骨作用。(C)2009 Elsevier Inc. All rights reserved.
HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro.The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and mu-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed.In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, Suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results Suggest that HB-GAM is all osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone. (C) 2009 Elsevier Inc. All rights reserved.