ArticleThe Journal of biological chemistry2010
CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 119 citations in OpenAlex.
- Stromal CYR61 Confers Resistance to Mitoxantrone via Spleen Tyrosine Kinase Activation in Human Acute Myeloid Leukaemia.British journal of haematology · 2015Trial
- Integrin αVβ3 as a context‑dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review).Molecular medicine reports · 2026Review
- Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low-intensity pulsed ultrasound and bone morphogenetic protein 2.Journal of cell communication and signaling · 2026Article
- Identification of Genes Related to Rapid Growth of Giant Grouper (Animals : an open access journal from MDPI · 2025Article
- The biological function of integrin-linked kinase on bone formation.Bone reports · 2025Review
- CYR61 delivery promotes angiogenesis during bone fracture repair.NPJ Regenerative medicine · 2025Article
- ECM Protein CYR61 Promotes Migration and Osteoblastic Differentiation of Irradiation BMSCs via Migrasomes.Stem cells international · 2025Article
- Eucommia ulmoides Oliver polysaccharide alleviates glucocorticoid-induced osteoporosis by stimulating bone formation via ERK/BMP-2/SMAD signaling.Scientific reports · 2024Article
- Well-known polypeptides of deer antler velvet with key actives: modern pharmacological advances.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Astragaloside IV improves pulmonary arterial hypertension by increasing the expression of CCN1 and activating the ERK1/2 pathway.Journal of cellular and molecular medicine · 2023Article
- Controversial causal association between IGF family members and osteoporosis: a Mendelian randomization study between UK and FinnGen biobanks.Frontiers in endocrinology · 2023Article
- Inhibition of SRC-mediated integrin signaling in bone marrow niche enhances hematopoietic stem cell function.iScience · 2022Article
- 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
- CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation.Nature communications · 2022Article
- Sclareol inhibits RANKL-induced osteoclastogenesis and promotes osteoblastogenesis through promoting CCN1 expression via repressing the MAPK pathway.Cell biology and toxicology · 2021Article
- Thymoquinone loading into hydroxyapatite/alginate scaffolds accelerated the osteogenic differentiation of the mesenchymal stem cells.Biomedical engineering online · 2021Article
- Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.International journal of molecular sciences · 2020Review
- Article
- Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors.International journal of molecular sciences · 2020Article
- 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
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoporosis is one of the most common bone pathologies. A number of novel molecules have been reported to increase bone formation including cysteine-rich protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear. It is known that bone morphogenetic proteins (BMPs), especially BMP-2, are crucial regulators of osteogenesis. However, the interaction between CYR61 and BMP-2 is unclear. We found that CYR61 significantly increases proliferation and osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in a time- and dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic differentiation are significantly decreased by knockdown of BMP-2 expression or inhibition of BMP-2 activity. In this study we found integrin α(v)β(3) is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that integrin-linked kinase, which is downstream of the α(v)β(3) receptor, is involved in CYR61-induced BMP-2 expression and subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken together, our results show that CYR61 up-regulates BMP-2 mRNA and protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the α(v)β(3) integrin/integrin-linked kinase/ERK signaling pathway.
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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.