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]
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“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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Self-citation
Research works printed but not linked: 3
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Street, J., Bao, M., Deguzman, L., Bunting, S., Peale, F. V., Jr., Ferrara, N., Steinmetz, H., Hoeffel, J. M., Cleland, J. L., Daugherty, A. L., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152324099 · Cited by 1,402
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The pathophysiology of endometriosis and adenomyosis, tissue injury and repair
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“Following termination of unphysiological strain and healing, this process is down-regulated and the local production of estrogen or up-regulation of estrogendependent genes ceases [54, 57 ].”
BackgroundNOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues
Perbal, B. (2001) · Molecular Pathology · doi:10.1136/mp.54.2.57 · Cited by 345
CCN1/CYR61: the very model of a modern matricellular protein
Lau, L. F. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0778-3 · Cited by 338
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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