ArticleProceedings of the National Academy of Sciences of the United States of America2018
Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Current state of bioceramic bone repair materials in immune regulation: a review.Frontiers of medicine · 2025Review
- Effects of calcium-sensitive receptors on chondrogenic differentiation of rat bone marrow mesenchymal stem cells.Cell and tissue banking · 2025Article
- Biodentine Stimulates Calcium-Dependent Osteogenic Differentiation of Mesenchymal Stromal Cells from Periapical Lesions.International journal of molecular sciences · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Signaling Dynamics in Osteogenesis: Unraveling Therapeutic Targets for Bone Generation.Current drug targets · 2025Review
- Bio-integrated scaffold facilitates large bone regeneration dominated by endochondral ossification.Bioactive materials · 2024Article
- Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Stimulation of Metabolic Activity and Cell Differentiation in Osteoblastic and Human Mesenchymal Stem Cells by a Nanohydroxyapatite Paste Bone Graft Substitute.Materials (Basel, Switzerland) · 2022Article
- Directed Regeneration of Osteochondral Tissue by Hierarchical Assembly of Spatially Organized Composite Spheroids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Biobridge: An Outlook on Translational Bioinks for 3D Bioprinting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Early Addition of Parathyroid Hormone-Related Peptide Regulates the Hypertrophic Differentiation of Mesenchymal Stem Cells.Cartilage · 2021Article
- Encapsulated Mesenchymal Stromal Cell Microbeads Promote Endogenous Regeneration of Osteoarthritic Cartilage Ex Vivo.Advanced healthcare materials · 2021Article
- Turning Nature's own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering.Advanced drug delivery reviews · 2021Review
- Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis.EMBO molecular medicine · 2020Article
- The Incorporation of Marine Coral Microparticles into Collagen-Based Scaffolds Promotes Osteogenesis of Human Mesenchymal Stromal Cells via Calcium Ion Signalling.Marine drugs · 2020Article
- Deficiency of Calcitonin Gene-Related Peptide Affects Macrophage Polarization in Osseointegration.Frontiers in physiology · 2020Article
- Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis.Stem cell research & therapy · 2019Article
- Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In adult bone injuries, periosteum-derived mesenchymal stem/stromal cells (MSCs) form bone via endochondral ossification (EO), whereas those from bone marrow (BM)/endosteum form bone primarily through intramembranous ossification (IMO). We hypothesized that this phenomenon is influenced by the proximity of MSCs residing in the BM to the trabecular bone microenvironment. Herein, we investigated the impact of the bone mineral phase on human BM-derived MSCs' choice of ossification pathway, using a biomimetic bone-like hydroxyapatite (BBHAp) interface. BBHAp induced hyperstimulation of extracellular calcium-sensing receptor (CaSR) and temporal down-regulation of parathyroid hormone 1 receptor (PTH1R), leading to inhibition of chondrogenic differentiation of MSCs even in the presence of chondroinductive factors, such as transforming growth factor-β1 (TGF-β1). Interestingly rescuing PTH1R expression using human PTH fragment (1-34) partially restored chondrogenesis in the BBHAp environment. In vivo studies in an ectopic site revealed that the BBHAp interface inhibits EO and strictly promotes IMO. Furthermore, CaSR knockdown (CaSR KD) disrupted the bone-forming potential of MSCs irrespective of the absence or presence of the BBHAp interface. Our findings confirm the expression of CaSR in human BM-derived MSCs and unravel a prominent role for the interplay between CaSR and PTH1R in regulating MSC fate and the choice of pathway for bone formation.
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