ArticleNature communications2021
RSPO3 is important for trabecular bone and fracture risk in mice and humans.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Role of Complement Component 9 in Bone Health: Causal Evidence in Humans and Mechanistic Studies in Mice.Calcified tissue international · 2026Article
- Identification of ephrin-A1-EphA2 signalling as a potential target for fracture prevention.Nature communications · 2026Article
- Facial skin aging is a potential osteoporosis-associated marker: evidence from both observational and genetic studies.Journal of bone and mineral metabolism · 2026Article
- Bone regeneration induced by a novel quercetin/a-CSH/n-HA composite in critical size tibia defect of rats with osteoporosis.Scientific reports · 2025Article
- Leveraging Proteomics and Proteogenomics for Understanding Osteoporosis and Other Musculoskeletal Diseases.Current osteoporosis reports · 2025Review
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology.Biomedicines · 2025Review
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- Combined application of mesenchymal stem cells and different glucocorticoid dosing alleviates osteoporosis in SLE murine models.Immunity, inflammation and disease · 2024Article
- SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals.Bioinformatics (Oxford, England) · 2024Article
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- An atlas of genetic determinants of forearm fracture.Nature genetics · 2023Article
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- Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing.Bone · 2023Article
- High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Genetic insight into the putative causal proteins and druggable targets of osteoporosis: a large-scale proteome-wide mendelian randomization study.Frontiers in genetics · 2023Article
- Article
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 9 countries.
Funding
Abstract
With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
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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 Socratic graph.