Cited by 198Bone Metabolism and DiseasesNeuropeptides and Animal PhysiologyBone health and osteoporosis research

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Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-κB activation, osteoclastogenesis and bone resorption

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Wang, Liping, Shi, Xiaoyou, Zhao, Rong, Halloran, Bernard P., Clark, David J., Jacobs, Christopher R., Kingery, Wade S.·2010·Bone

DOI 10.1016/j.bone.2009.11.029PMC PMC2854244

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Abstract

Previously we observed that capsaicin treatment in rats inhibited sensory neuropeptide signaling, with a concurrent reduction in trabecular bone formation and bone volume, and an increase in osteoclast numbers and bone resorption. Calcitonin gene-related peptide (CGRP) is a neuropeptide richly distributed in sensory neurons innervating the skeleton and we postulated that CGRP signaling regulates bone integrity. In this study we examined CGRP effects on stromal and bone cell differentiation and activity in vitro. CGRP receptors were detected by immunocytochemical staining and real time PCR assays in mouse bone marrow stromal cells (BMSCs) and bone marrow macrophages (BMMs). CGRP effects on BMSC proliferation and osteoblastic differentiation were studied using BrdU incorporation, PCR products, alkaline phosphatase (ALP) activity, and mineralization assays. CGRP effects on BMM osteoclastic differentiation and activity were determined by quantifying tartrate-resistant acid phosphatase positive (TRAP+) multinucleated cells, pit erosion area, mRNA levels of TRAP and cathepsin K, and nuclear factor-κB (NF-κB) nuclear localization. BMSCs, osteoblasts, BMMs, and osteoclasts all expressed CGRP receptors. CGRP (10-10-10-8M) stimulated BMSC proliferation, up-regulated the expression of osteoblastic genes, and increased ALP activity and mineralization in the BMSCs. In BMM cultures CGRP (10-8M) inhibited receptor activator of NF-κB ligand (RANKL) activation of NF-κB. CGRP also down-regulated osteoclastic genes like TRAP and cathepsin K, decreased the numbers of TRAP+ cells, and inhibited bone resorption activity in RANKL stimulated BMMs. These results suggest that CGRP signaling maintains bone mass both by directly stimulating stromal cell osteoblastic differentiation and by inhibiting RANKL induced NF-κB activation, osteoclastogenesis, and bone resorption.

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Authors: Wang, L., Shi, X., Zhao, R., Halloran, B. P., Clark, D. J., Jacobs, C. R., & Kingery, W. S.
Affiliations: VA Palo Alto Health Care System (US)
San Francisco VA Medical Center (US)
Corresponding author: Wang, Liping
ORCID: Wang, Liping
Shi, Xiaoyou
Zhao, Rong
Jacobs, Christopher R.
Kingery, Wade S.
Venue: Bone
Publisher: Elsevier BV
Published: 2010-05
Volume: 46
Issue: 5
Pages: 1369-1379
ISSN: 1873-2763 (ISSN-L)
8756-3282
DOI: 10.1016/j.bone.2009.11.029
PMC: PMC2854244
OpenAlex: W2039009902
Semantic Scholar: 97501e887b43c9d591e6450a3690e83b185845cc
Cited by: 198
References: 53
Citations by year: 2026: 11 · 2025: 17 · 2024: 16 · 2023: 19 · 2022: 16 · 2021: 8 · 2020: 17 · 2019: 18 · 2018: 18 · 2017: 10 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 10 · 2012: 3
FWCI: 1.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Bone (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (A4265R)
National Institute of Diabetes and Digestive and Kidney Diseases (DK067197)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: calcitonin gene-related peptide, mesenchymal stem cells, osteogenic differentiation, osteoclastogenesis, bone resorption, RANKL, NF-κB activation, bone marrow-derived macrophages, CGRP receptor, sensory neuropeptides, bone mass regulation, capsaicin, cathepsin K, traps
MeSH terms: Alkaline Phosphatase, Animals, Bone Resorption, Cell Differentiation, Cells, Cultured, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Osteoclasts, Osteogenesis, Blotting, Western, Calcitonin Gene-Related Peptide, Polymerase Chain Reaction, NF-kappa B, Stromal Cells, Microscopy, Confocal, Cell Proliferation, Mice, RANK Ligand

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Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-κB activation, osteoclastogenesis and bone resorption

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