Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network
Year: 2026
Type: article
Abstract: Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues. Classically, cartilage and bone formation have been considered independent processes at cellular level. However, the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells, or chondrocyte-derived osteoblasts. We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events. First, the process was assessed in mouse bone tissue, and then, it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols. Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation. This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols. Gene expression profiling reveals that NOTCH, BMP and MAPK signaling pathways are relevant at the phenotype-switch, while the transcription factors Mesp1, Alx1, Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation. Altogether, this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events, previously described at skeleton morphogenesis during embryo development, and from now on also linkable to postnatal bone development and regeneration processes.
Source: Bone Research
Authors: Raquel Ruiz-Hernández, Laurie Gay, Verónica Moncho-Amor, Pablo Martín, Jhonatan A. Vergara-Arce, Stefania Di Blasio, Thomas Snoeks, Unai Cossío, Ander Matheu, Maria M. Caffarel, Daniela Gerovska, Marcos J. Araúzo-Bravo, Amaia Vilas, Felipe Prosper, Sergio Moya, Daniel Alonso-Alconada, Ana Alonso-Varona, Gretel Nusspaumer, Javier Lopez-Rios, Karine Rizotti, Robin Lovell-Badge, Dominique Bonnet, Ilaria Malanchi, Ander Abarrategi
Institutions: University of the Basque Country, CIC biomaGUNE, The Francis Crick Institute, Biogipuzkoa Health Research Institute, University of Chieti-Pescara, Ikerbasque, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Navarre Institute of Health Research, Centro de Investigación Médica Aplicada, Centro de Investigación Biomédica en Red de Cáncer, Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,405
Awards: G1175115578, G1205047551, G1255370140, G1622782223, G2261121936, G2262748287, G2292173875, G2365507271, G2672435700, G300979063, G3113808516, G34346518, G3480869486, G410571670, G425668148, G451917667, G4539932019, G5080475149, G540885125, G546112533, G5539308778, G5967599077, G6218905885, G6298273575, G7084143925, G774498915, G8696694383, G8888022036, G929308097
OpenAlex ID: W7128438646