LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

作     者：Changjun Li Bart O Williams Xu Cao Mei Wan 

作者机构：Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Center for Skeletal Disease and Tumor Metastasis and Laboratory of Cell Signaling and Carcinogenesis Van Andel Research Institute 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2014年第2卷第1期

页      面：43-54页

核心收录：

学科分类：1002[医学-临床医学] 1010[医学-医学技术（可授医学、理学学位）] 100215[医学-康复医学与理疗学] 10[医学] 

基　　金：supported by National Institutes of Health Grant DK083350 to M. W 

主　　题：bone LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling stem 

摘      要：Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ MSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.