Cited by 110Connective Tissue Growth Factor ResearchBone fractures and treatmentsBone Tumor Diagnosis and Treatments

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Temporal Expression of the Chondrogenic and Angiogenic Growth Factor CYR61 During Fracture Repair

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Hadjiargyrou, Michael, Ahrens, William, Rubin, Clinton T.·2000·Journal of Bone and Mineral Research

DOI 10.1359/jbmr.2000.15.6.1014

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Abstract

The repair of a fractured bone is a complex biological event that essentially recapitulates embryonic development and requires the activity of a number of different cell types undergoing proliferation, migration, adhesion, and differentiation, while at the same time expressing a host of different genes. To identify such genes, we employed differential display and compared messenger RNA (mRNA) populations isolated from postfracture (PF) day 5 calluses to those of intact rat femurs. One such gene in which expression was up-regulated at PF day 5 is identified as CYR61, a member of the CCN family of secreted regulatory proteins. CYR61 is a growth factor that stimulates chondrogenesis and angiogenesis. We show that its mRNA expression during fracture repair is regulated temporally, with elevated levels seen as early as PF day 3 and day 5, rising dramatically at PF day 7 and day 10, and finally declining at PF day 14 and day 21. At the highest peak of expression (PF day 7 and day 10, which correlates with chondrogenesis), CYR61 mRNA levels are approximately 10-fold higher than those detected in intact femurs. Similarly, high protein levels are detected throughout the reparative phase of the callus, particularly in fibrous tissue and periosteum, and in proliferating chondrocytes, osteoblasts, and immature osteocytes. The secreted form of CYR61 also was detected within the newly made osteoid. No labeling was detected in hypertrophic chondrocytes or in mature cortical osteocytes. These results suggest that CYR61 plays a significant role in cartilage and bone formation and may serve as an important regulator of fracture healing.

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Authors: Hadjiargyrou, M., Ahrens, W., & Rubin, C. T.
Affiliations: Stony Brook University (US)
Corresponding author: Hadjiargyrou, Michael
ORCID: Hadjiargyrou, Michael
Rubin, Clinton T.
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 2000-06-01
Volume: 15
Issue: 6
Pages: 1014-1023
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1359/jbmr.2000.15.6.1014
OpenAlex: W2074426211
Cited by: 110
References: 29
Citations by year: 2026: 3 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 9 · 2014: 3 · 2013: 3 · 2012: 4
FWCI: 2.17
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Journal of Bone and Mineral Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone fractures and treatments
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
Keywords: CYR61, CCN family, fracture healing, callus, chondrogenesis, angiogenesis, temporal gene expression, mRNA expression, osteoblasts, chondrocytes, osteoid, periosteum, rat femur, secreted growth factors
MeSH terms: Animals, Base Sequence, Bony Callus, Collagen, Femoral Fractures, Femur, Gene Expression Regulation, Growth Substances, Male, Molecular Sequence Data, Neovascularization, Pathologic, RNA, Messenger, Fracture Healing, Rats, Sprague-Dawley, Immediate-Early Proteins, Chondrogenesis, Intercellular Signaling Peptides and Proteins, Rats, Cysteine-Rich Protein 61

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Temporal Expression of the Chondrogenic and Angiogenic Growth Factor CYR61 During Fracture Repair

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