The DOI matches its Crossref record; 27 of the 29 references it cites were found in a registry or an index.
Temporal Expression of the Chondrogenic and Angiogenic Growth Factor CYR61 During Fracture Repair
Open accessAbstract
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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“In addition to cutaneous wound healing, CCN1 expression is elevated in remodeling cardiomyocytes after myocardial infarctions [24], in vascular injury [56], and in the long bones during fracture repair, notably in proliferating chondrocytes and osteoblasts [127,128].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [127]
In the citing paper
“Following termination of unphysiological strain and healing, this process is down-regulated and the local production of estrogen or up-regulation of estrogen-dependent genes ceases [54, 57].”
From The pathophysiology of endometriosis and adenomyosis, tissue injury and repair (2009) · cites this paper as [57]
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Cites
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Research works printed but not linked: 3
- Hadjiargyrou, 1997, The temporal expression of osteopontin mRNA in the fracture callus is altered by low intensity ultrasound, J Bone Miner Res, 12, S290
- Hadjiargyrou, 1998, Differential gene expression during the early stages of fracture healing, Bone, 23, S235
- Hadjiargyrou, 1999, Upregulation of a novel and several known genes during the early phases of fracture healing, J Bone Miner Res, 14, S438
Cited by
Sorted by citations
Items 101–110 of 110
CCN (C YR 61, C TGF , N OV ) Gene Family
Lau, L. F. (2002) · Wiley eBooks · doi:10.1002/0471203076.emm0702
Tissue Regeneration in Dentistry
Tanne, K., Papagerakis, P., Papaccio, G., Kitamura, C., & Tanimoto, K. (2012) · International Journal of Dentistry · doi:10.1155/2012/586701
Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering
Ravi, S. (2010) · SMARTech Repository (Georgia Institute of Technology)
(2009) · Wiley eBooks · doi:10.1002/9780470824023.refs
The effect of soft tissue defect on callus formation in Kunming mice different tibial injury modelsPreprint
Liu, L., Cai, B., Liu, L., Zhuang, X., Wu, Y., & Zhang, J. (2022) · Research Square · doi:10.21203/rs.3.rs-2006802/v1
Osteocyte-vascular Interactions in Bone Physiology and Pathology
Gellée, L., & Maurel, D. B. (2026) · Current Osteoporosis Reports · doi:10.1007/s11914-026-00978-x
Tran, A. B., & Ortiz-Hernández, G. L. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1843283
Blackwood, D. J., Xu, J., & Mei, D. (2026) · Elsevier eBooks · doi:10.1016/b978-0-323-91239-6.00008-3
Komuro (2001) · doi:10.1002/1529-0131(200112)44:12
Metadata
- Authors
- Hadjiargyrou, M., Ahrens, W., & Rubin, C. T.
- Affiliations
- Stony Brook University (US)
- Corresponding author
- Hadjiargyrou, Michael
- 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
- 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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