MCP-1 Expression Is Specifically Regulated During Activation of Skeletal Repair and Remodeling

Wu, A. C.; Morrison, N. A.; Kelly, W. L.; Forwood, M. R.

doi:10.1007/s00223-013-9718-6

Cited by 51Bone Metabolism and DiseasesChemokine receptors and signalingBone fractures and treatments

MCP-1 Expression Is Specifically Regulated During Activation of Skeletal Repair and Remodeling

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Wu, A. C., Morrison, N. A., Kelly, W. L., Forwood, M. R.·2013·Calcified Tissue International

DOI 10.1007/s00223-013-9718-6

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Abstract

Monocyte chemotactic protein-1 (MCP-1) belongs to the CC chemokine superfamily and plays a critical role in the recruitment and activation of leukocytes during acute inflammation. We hypothesize that MCP-1 is also an important chemokine that regulates the recruitment and activation of bone cells required for skeletal repair and remodeling. We used the ulnar stress fracture (SFx) model, which allows investigation of focal remodeling with a known time course and precise anatomical location. SFx were created in the right ulna of female Wistar rats using cyclic end loading. Unloaded animals were used as a control. Rats were killed 4 h and 1, 4, 7, and 14 days after loading (n = 10/group); RNA was extracted and converted to cDNA for quantitative PCR analysis using TaqMan gene expression assays. Four hours after loading, MCP-1 gene expression was increased ~30-fold (P < 0.001), remained elevated at 24 h (~12-fold, P < 0.001), then declined by day 14. Relative to the contralateral limb, expression of the receptors CCR1 and CCR2 increased over the 14 days, being significant by 4 days for CCR1 and 14 days for CCR2 (P < 0.05). Other inflammation-related chemokines (RANTES, MIP1a) were not increased at these early time points. Using in situ hybridization and immunohistochemistry in separate animal groups (n = 5/group, control, days 1, 4, 7), MCP-1 mRNA and protein were localized in periosteal osteoblasts associated with woven bone formation at the fracture exit point but not in osteocytes adjacent to the SFx. These data support an important role for MCP-1 in the early phase of SFx repair and activated remodeling.

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In bones subjected to fatigue loading, viable osteocytes near apoptotic ones express high RANKL/OPG ratio and increased VEGF and CCL2, promoting increased local osteoclastogenesis.
“For instance, in bones subjected to fatigue loading, viable osteocytes near the apoptotic ones express, besides high RANKL/OPG ratio, increased levels of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (CCL2) promoting an increase in local osteoclastogenesis [194, 195].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [195]

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Authors: Wu, A. C., Morrison, N. A., Kelly, W. L., & Forwood, M. R.
Affiliations: Griffith University (AU)
Corresponding author: Forwood, M. R.
ORCID: Wu, A. C.
Kelly, W. L.
Forwood, M. R.
Venue: Calcified Tissue International
Publisher: Springer Science and Business Media LLC
Published: 2013-03-05
Volume: 92
Issue: 6
Pages: 566-575
ISSN: 0171-967X (ISSN-L)
1432-0827
DOI: 10.1007/s00223-013-9718-6
OpenAlex: W2049290532
Cited by: 51
References: 31
Citations by year: 2026: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 2
FWCI: 2.69
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: www.springer.com/tdm (tdm)
Locations: Calcified Tissue International (publishedVersion)
PubMed (publishedVersion)
Griffith Research Online (submittedVersion)
Funders: Griffith University
Medical Research Council
National Health and Medical Research Council (597481, 511187)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
Keywords: MCP-1, bone remodeling, skeletal repair, CC chemokines, CCR1, CCR2, woven bone formation, fracture healing, chemokine expression, bone inflammation
MeSH terms: Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Fractures, Stress, Bone Remodeling, Fracture Healing, Rats, Wistar, In Situ Hybridization, Chemokine CCL2, Reverse Transcriptase Polymerase Chain Reaction, Rats, Transcriptome, Real-Time Polymerase Chain Reaction

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MCP-1 Expression Is Specifically Regulated During Activation of Skeletal Repair and Remodeling

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