ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2018
CYR61/CCN1 Regulates Sclerostin Levels and Bone Maintenance.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- CCN1 as a compartment-specific biomarker of active microenvironmental remodeling: evidence from bone repair, aging, inflammation, and cancer.Frontiers in medicine · 2026Review
- Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices.International journal of molecular sciences · 2025Article
- CCN Proteins as Matricellular Regulators of Bone in Aging and Disease.Current osteoporosis reports · 2025Review
- CYR61 delivery promotes angiogenesis during bone fracture repair.NPJ Regenerative medicine · 2025Article
- Microstructural and transcriptomic characterization of trabecular bone in idiopathic osteonecrosis of the femoral head.Scientific reports · 2025Article
- Role of YAP/TAZ in bone diseases: A transductor from mechanics to biology.Journal of orthopaedic translation · 2025Review
- A glucocorticoid spike derails muscle repair to heterotopic ossification after spinal cord injury.Cell reports. Medicine · 2024Article
- Hypoxia-initiated Cysteine-rich protein 61 secretion promotes chemoresistance of acute B lymphoblastic leukemia cells.American journal of cancer research · 2024Article
- Decrease of Cellular Communication Network Factor 1 (CCN1) Attenuates PTZ-Kindled Epilepsy in Mice.Cellular and molecular neurobiology · 2023Article
- The regulation and functions of the matricellular CCN proteins induced by shear stress.Journal of cell communication and signaling · 2023Review
- GRP78 promotes the osteogenic and angiogenic response in periodontal ligament stem cells.European cells & materials · 2023Article
- Myeloid CCN3 protects against aortic valve calcification.Cell communication and signaling : CCS · 2023Article
- Controversial causal association between IGF family members and osteoporosis: a Mendelian randomization study between UK and FinnGen biobanks.Frontiers in endocrinology · 2023Article
- Matrix-bound Cyr61/CCN1 is required to retain the properties of the bone marrow mesenchymal stem cell niche but is depleted with aging.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Article
- CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.Journal of cell communication and signaling · 2021Review
- Plasminogen Regulates Fracture Repair by Promoting the Functions of Periosteal Mesenchymal Progenitors.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration.Materials today. Bio · 2021Review
- CCN1/Cyr61 Is Required in Osteoblasts for Responsiveness to the Anabolic Activity of PTH.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Native extracellular matrix, synthesized ex vivo by bone marrow or adipose stromal cells, faithfully directs mesenchymal stem cell differentiation.Matrix biology plus · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone-specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermates. Our data suggest that CYR61/CCN1 exerts its effects on mature osteoblast/osteocyte function to modulate bone mass. Specifically, changes were observed in osteocyte/osteoblast expression of RankL, VegfA, and Sost. The increase in RankL expression was correlated with a significant increase in osteoclast number; decreased VegfA expression was correlated with a significant decrease in bone vasculature; increased Sost expression was associated with decreased Wnt signaling, as revealed by decreased Axin2 expression and increased adiposity in the bone marrow. Although the decreased number of vascular elements in bone likely contributes to the low bone mass phenotype in Cyr61 conditional knockout mice, this cannot explain the observed increase in osteoclasts and the decrease in Wnt signaling. We conducted in vitro assays using UMR-106 osteosarcoma cells to explore the role CYR61/CCN1 plays in modulating Sost mRNA and protein expression in osteocytes and osteoblasts. Overexpression of CYR61/CCN1 can suppress Sost expression in both control and Cyr61 knockout cells, and blocking Sost with siRNA can rescue Wnt responsiveness in Cyr61 knockout cells in vitro. Overall, our data suggest that CYR61/CCN1 modulates mature osteoblast and osteocyte function to regulate bone mass through angiogenic effects as well as by modulating Wnt signaling, at least in part through the Wnt antagonist Sost. © 2018 American Society for Bone and Mineral Research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.