PMID- 20819641 OWN - NLM STAT- MEDLINE DCOM- 20101223 LR - 20181201 IS - 2542-5641 (Electronic) IS - 0366-6999 (Linking) VI - 123 IP - 13 DP - 2010 Jul TI - Calcitonin gene-related peptide induces proliferation and monocyte chemoattractant protein-1 expression via extracellular signal-regulated kinase activation in rat osteoblasts. PG - 1748-53 AB - BACKGROUND: Calcitonin gene-related peptide (CGRP), a sensory neuropeptide, affects osteoblast proliferation and bone formation. However, the mechanisms are not fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that stimulates the migration of monocytes and plays important roles in regulating bone remolding during fracture repair. In this study, we investigated the effects of CGRP on proliferation and MCP-1 expression in cultured rat osteoblasts. METHODS: Primary rat osteoblasts were isolated from fetal rats calvariae. Cells were exposed to gradient concentrations (10(-9) to 10(-7) mol/L) of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and semiquantitative reverse transcription-polymerase chain reaction, respectively. The protein level of MCP-1 was investigated and compared in cell culture media by enzyme linked immunosorbent assay (ELISA). Phospho-extracellular signal-regulated kinase (ERK) expression was detected by Western blotting. Cell proliferative activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and BrdU assay. The effects of MAPK/ERK kinase (MEK)-inhibitor U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined. RESULTS: CGRP effectively enhanced primary rat osteoblast proliferation and led to significant increases in the expression of MCP-1 mRNA and protein in time- and dose-dependent manners. CGRP activated the ERK pathway. Pretreatment of cultured rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell proliferation and stimulated MCP-1 expression in cultured rat osteoblasts. CONCLUSION: These studies document novel links between CGRP and MCP-1 and illuminate the effects of CGRP in regulating bone remodeling. FAU - Han, Na AU - Han N AD - Department of Orthopaedics and Trauma, Peking University People's Hospital, Beijing 100044, China. FAU - Zhang, Dian-Ying AU - Zhang DY FAU - Wang, Tian-Bing AU - Wang TB FAU - Zhang, Pei-Xun AU - Zhang PX FAU - Jiang, Bao-Guo AU - Jiang BG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Butadienes) RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Nitriles) RN - 0 (U 0126) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Animals MH - Blotting, Western MH - Butadienes/pharmacology MH - Calcitonin Gene-Related Peptide/*pharmacology MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*metabolism MH - Nitriles/pharmacology MH - Osteoblasts/*drug effects/*metabolism MH - Rats EDAT- 2010/09/08 06:00 MHDA- 2010/12/25 06:00 CRDT- 2010/09/08 06:00 PHST- 2010/09/08 06:00 [entrez] PHST- 2010/09/08 06:00 [pubmed] PHST- 2010/12/25 06:00 [medline] PST - ppublish SO - Chin Med J (Engl). 2010 Jul;123(13):1748-53.