ArticleInternational journal of molecular sciences2017
Evidence of the Role of R-Spondin 1 and Its Receptor Lgr4 in the Transmission of Mechanical Stimuli to Biological Signals for Bone Formation.
Article in International journal of molecular sciences, 2017. 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, 47 citations in OpenAlex.
- PCBP2 as an intrinsic agi ng factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis.eLife · 2025Article
- LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology.Biomedicines · 2025Review
- The role of LGR4 in bone metabolism and tumor bone metastasis.Frontiers in endocrinology · 2025Review
- Article
- An LGR4 agonist activates the GSK‑3β pathway to inhibit RANK‑RANKL signaling during osteoclastogenesis in bone marrow‑derived macrophages.International journal of molecular medicine · 2024Article
- Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms.Bone research · 2023Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Integrating physicomechanical and biological strategies for BTE: biomaterials-induced osteogenic differentiation of MSCs.Theranostics · 2023Review
- Article
- Article
- The Wnt pathway: An important control mechanism in bone's response to mechanical loading.Bone · 2021Review
- Serum exosomes from young rats improve the reduced osteogenic differentiation of BMSCs in aged rats with osteoporosis after fatigue loading in vivo.Stem cell research & therapy · 2021Article
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Nicotinamide mononucleotide attenuates glucocorticoid‑induced osteogenic inhibition by regulating the SIRT1/PGC‑1α signaling pathway.Molecular medicine reports · 2020Article
- The Bone Extracellular Matrix in Bone Formation and Regeneration.Frontiers in pharmacology · 2020Review
- The Regulation of Bone Metabolism and Disorders by Wnt Signaling.International journal of molecular sciences · 2019Review
- Apoptosis of mesenchymal stem cells is regulated byChronic diseases and translational medicine · 2019Article
- MicroRNA-92a-1-5p influences osteogenic differentiation of MC3T3-E1 cells by regulating β-catenin.Journal of bone and mineral metabolism · 2019Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bone can adjust its mass and architecture to mechanical stimuli via a series of molecular cascades, which have been not yet fully elucidated. Emerging evidence indicated that R-spondins (Rspos), a family of secreted agonists of the Wnt/β-catenin signaling pathway, had important roles in osteoblastic differentiation and bone formation. However, the role of Rspo proteins in mechanical loading-influenced bone metabolism has never been investigated. In this study, we found that Rspo1 was a mechanosensitive protein for bone formation. Continuous cyclic mechanical stretch (CMS) upregulated the expression of Rspo1 in mouse bone marrow mesenchymal stem cells (BMSCs), while the expression of Rspo1 in BMSCs in vivo was downregulated in the bones of a mechanical unloading mouse model (tail suspension (TS)). On the other hand, Rspo1 could promote osteogenesis of BMSCs under CMS through activating the Wnt/β-catenin signaling pathway and could rescue the bone loss induced by mechanical unloading in the TS mice. Specifically, our results suggested that Rspo1 and its receptor of leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) should be a novel molecular signal in the transmission of mechanical stimuli to biological signal in the bone, and this signal should be in the upstream of Wnt/β-catenin signaling for bone formation. Rspo1/Lgr4 could be a new potential target for the prevention and treatment of disuse osteoporosis in the future.
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