The Expression of Osteoprotegerin and RANK Ligand and the Support of Osteoclast Formation by Stromal-Osteoblast Lineage Cells Is Developmentally Regulated Export

@article{citeulike:3744407, abstract = {The one or more molecular mechanisms that determine the obligatory sequence of resorption followed by formation during bone remodeling is unclear. RANK ligand (RANK-L) is an essential requirement for osteoclastogenesis, and its activity is neutralized by binding to the soluble decoy receptor, osteoprotegerin (OPG). Because both molecules are produced by osteoblast lineage cells, we studied their developmental regulation in a conditionally immortalized human marrow stromal (hMS[2-15]) cell line. These cells can simulate the complete developmental sequence from undifferentiated precursor(s) to cells with the complete osteoblast phenotype that are capable of forming mineralized nodules. During osteoblast differentiation, RANK-L messenger RNA levels decreased by 5-fold, whereas OPG messenger RNA levels increased by 7-fold, resulting in a 35-fold change in the RANK-L/OPG ratio. OPG protein also increased by 6-fold. Mouse bone marrow cells generated osteoclast-like cells in coculture with undifferentiated hMS(2-15) cells, but did not when cocultured with hMS(2-15) cells in varying stages of differentiation, unless an excess of RANK-L was added. Thus, undifferentiated marrow stromal cells with a high RANK-L/OPG ratio can initiate and support osteoclastogenesis, but after differentiation to the mature osteoblast phenotype, they cannot. We speculate that the developmental regulation of OPG and RANK-L production by stromal/osteoblast cells contributes to the coordinated sequence of osteoclast and osteoblast differentiation during the bone remodeling cycle. 10.1210/en.141.12.4768}, author = {Gori, Francesca and Hofbauer, Lorenz C. and Dunstan, Colin R. and Spelsberg, Thomas C. and Khosla, Sundeep and Riggs, Lawrence B.}, citeulike-article-id = {3744407}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/en.141.12.4768}, citeulike-linkout-1 = {http://endo.endojournals.org/cgi/content/abstract/141/12/4768}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11108292}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11108292}, day = {1}, doi = {10.1210/en.141.12.4768}, journal = {Endocrinology}, keywords = {opg, osteoblast, osteoclast, rankl, time-delay}, month = {December}, number = {12}, pages = {4768--4776}, posted-at = {2008-12-04 04:11:52}, priority = {2}, title = {The Expression of Osteoprotegerin and RANK Ligand and the Support of Osteoclast Formation by Stromal-Osteoblast Lineage Cells Is Developmentally Regulated}, url = {http://dx.doi.org/10.1210/en.141.12.4768}, volume = {141}, year = {2000} }

TY - JOUR ID - citeulike:3744407 L3 - citeulike-article-id:3744407 N2 - The one or more molecular mechanisms that determine the obligatory sequence of resorption followed by formation during bone remodeling is unclear. RANK ligand (RANK-L) is an essential requirement for osteoclastogenesis, and its activity is neutralized by binding to the soluble decoy receptor, osteoprotegerin (OPG). Because both molecules are produced by osteoblast lineage cells, we studied their developmental regulation in a conditionally immortalized human marrow stromal (hMS[2-15]) cell line. These cells can simulate the complete developmental sequence from undifferentiated precursor(s) to cells with the complete osteoblast phenotype that are capable of forming mineralized nodules. During osteoblast differentiation, RANK-L messenger RNA levels decreased by 5-fold, whereas OPG messenger RNA levels increased by 7-fold, resulting in a 35-fold change in the RANK-L/OPG ratio. OPG protein also increased by 6-fold. Mouse bone marrow cells generated osteoclast-like cells in coculture with undifferentiated hMS(2-15) cells, but did not when cocultured with hMS(2-15) cells in varying stages of differentiation, unless an excess of RANK-L was added. Thus, undifferentiated marrow stromal cells with a high RANK-L/OPG ratio can initiate and support osteoclastogenesis, but after differentiation to the mature osteoblast phenotype, they cannot. We speculate that the developmental regulation of OPG and RANK-L production by stromal/osteoblast cells contributes to the coordinated sequence of osteoclast and osteoblast differentiation during the bone remodeling cycle. 10.1210/en.141.12.4768 IS - 12 JF - Endocrinology EP - 4776 TI - The Expression of Osteoprotegerin and RANK Ligand and the Support of Osteoclast Formation by Stromal-Osteoblast Lineage Cells Is Developmentally Regulated VL - 141 SP - 4768 KW - opg KW - osteoblast KW - osteoclast KW - rankl KW - time-delay AU - Gori, Francesca AU - Hofbauer, Lorenz AU - Dunstan, Colin AU - Spelsberg, Thomas AU - Khosla, Sundeep AU - Riggs, Lawrence PY - 2000/12/01/ UR - http://dx.doi.org/10.1210/en.141.12.4768 ER -