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Time- and cell-specific activation of BMP signaling restrains chondrocyte hypertrophy.
- Source :
-
IScience [iScience] 2024 Jul 18; Vol. 27 (8), pp. 110537. Date of Electronic Publication: 2024 Jul 18 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Stem cell therapies for degenerative cartilage disease are limited by an incomplete understanding of hyaline cartilage formation and maintenance. Human bone marrow stromal cells/skeletal stem cells (hBMSCs/SSCs) produce stable hyaline cartilage when attached to hyaluronic acid-coated fibrin microbeads (HyA-FMBs), yet the mechanism remains unclear. In vitro , hBMSC/SSC/HyA-FMB organoids exhibited reduced BMP signaling early in chondrogenic differentiation, followed by restoration of BMP signaling in chondrogenic IGFBP5 <superscript> + </superscript> / MGP <superscript> + </superscript> cells. Subsequently, human-induced pluripotent stem cell (hiPSC)-derived sclerotome cells were established (BMP inhibition) and then treated with transforming growth factor β (TGF-β) -/+ BMP2 and growth differentiation factor 5 (GDF5) (BMP signaling activation). TGF-β alone elicited a weak chondrogenic response, but TGF-β/BMP2/GDF5 led to delamination of SOX9 <superscript>+</superscript> aggregates (chondrospheroids) with high expression of COL2A1 , ACAN , and PRG4 and minimal expression of COL10A1 and ALP in vitro . While transplanted hBMSCs/SSCs/HyA-FMBs did not heal articular cartilage defects in immunocompromised rodents, chondrospheroid-derived cells/HyA-FMBs formed non-hypertrophic cartilage that persisted until at least 5 months in vivo .<br />Competing Interests: P.G.R., S.A.K., R.G., A.H.-L., and J.F. have a patent on the hyaluronic-acid-coated fibrin microbeads (US Patent #1094021).
Details
- Language :
- English
- ISSN :
- 2589-0042
- Volume :
- 27
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- IScience
- Publication Type :
- Academic Journal
- Accession number :
- 39193188
- Full Text :
- https://doi.org/10.1016/j.isci.2024.110537