PMID- 17690108 OWN - NLM STAT- MEDLINE DCOM- 20071212 LR - 20220409 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 282 IP - 45 DP - 2007 Nov 9 TI - Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. PG - 33098-106 AB - The clinical findings that alendronate blunted the anabolic effect of human parathyroid hormone (PTH) on bone formation suggest that active resorption is involved and enhances the anabolic effect. PTH signals via its receptor on the osteoblast membrane, and osteoclasts are impacted indirectly via the products of osteoblasts. Microarray with RNA from rats injected with human PTH or vehicle showed a strong association between the stimulation of monocyte chemoattractant protein-1 (MCP-1) and the anabolic effects of PTH. PTH rapidly and dramatically stimulated MCP-1 mRNA in the femora of rats receiving daily injections of PTH or in primary osteoblastic and UMR 106-01 cells. The stimulation of MCP-1 mRNA was dose-dependent and a primary response to PTH signaling via the cAMP-dependent protein kinase pathway in vitro. Studies with the mouse monocyte cell line RAW 264.7 and mouse bone marrow proved that osteoblastic MCP-1 can potently recruit osteoclast monocyte precursors and facilitate receptor activator of NF-kappaB ligand-induced osteoclastogenesis and, in particular, enhanced fusion. Our model suggests that PTH-induced osteoblastic expression of MCP-1 is involved in recruitment and differentiation at the stage of multinucleation of osteoclast precursors. This information provides a rationale for increased osteoclast activity in the anabolic effects of PTH in addition to receptor activator of NF-kappaB ligand stimulation to initiate greater bone remodeling. FAU - Li, Xin AU - Li X AD - Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. FAU - Qin, Ling AU - Qin L FAU - Bergenstock, Marika AU - Bergenstock M FAU - Bevelock, Laura M AU - Bevelock LM FAU - Novack, Deborah V AU - Novack DV FAU - Partridge, Nicola C AU - Partridge NC LA - eng GR - DK 48109/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070809 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Parathyroid Hormone) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Animals MH - Cell Differentiation/drug effects MH - Cell Fusion MH - Cell Movement/drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/*metabolism/pharmacology MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Mice MH - Osteoblasts/cytology/*drug effects/*metabolism MH - Osteoclasts/cytology/*drug effects/*metabolism MH - Parathyroid Hormone/*pharmacology MH - RANK Ligand/pharmacology MH - RNA, Messenger/genetics MH - Rats MH - Signal Transduction EDAT- 2007/08/11 09:00 MHDA- 2007/12/13 09:00 CRDT- 2007/08/11 09:00 PHST- 2007/08/11 09:00 [pubmed] PHST- 2007/12/13 09:00 [medline] PHST- 2007/08/11 09:00 [entrez] AID - S0021-9258(20)61319-9 [pii] AID - 10.1074/jbc.M611781200 [doi] PST - ppublish SO - J Biol Chem. 2007 Nov 9;282(45):33098-106. doi: 10.1074/jbc.M611781200. Epub 2007 Aug 9.