RUNX2 is essential for maintaining synchondrosis chondrocytes and cranial base growth
Year: 2025
Type: article
Abstract: The cranial base synchondroses, comprised of opposite-facing bidirectional chondrocyte layers, drive anteroposterior cranial base growth. In humans, RUNX2 haploinsufficiency causes cleidocranial dysplasia associated with deficient midfacial growth. However, how RUNX2 regulates chondrocytes in the cranial base synchondroses remains unknown. To address this, we inactivated Runx2 in postnatal synchondrosis chondrocytes using a tamoxifen-inducible Fgfr3-creER (Fgfr3-Runx2cKO) mouse model. Fgfr3-Runx2cKO mice displayed skeletal dwarfism and reduced anteroposterior cranial base growth associated with premature synchondrosis ossification due to impaired chondrocyte proliferation, accelerated hypertrophy, apoptosis, and osteoclast-mediated cartilage resorption. Lineage tracing reveals that Runx2-deficient Fgfr3+ cells failed to differentiate into osteoblasts. Notably, Runx2-deficient chondrocytes showed an elevated level of FGFR3 and its downstream signaling components, pERK1/2 and SOX9, suggesting that RUNX2 downregulates FGFR3 in the synchondrosis. This study unveils a new role of Runx2 in cranial base chondrocytes, identifying a possible RUNX2-FGFR3-MAPK-SOX9 signaling axis that may control cranial base growth.
Source: Bone Research
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,405
Awards: G1097297626, NOVEL STRATEGY FOR BONE TISSUE ENGINEERING USING NANOFIBROUS OSTEOGENIC COLLAGEN PEPTIDES, G1287925916, G1819292872, G2688307317, Craniofacial skeletal cell lineage plasticity for reconstituting stem cells and their niches, Tissue Engineering and Regeneration, G4599319085, G4903648911, G5218993584, Dynamics and Regulations of Bone Stem Cells in Vivo, G7687712225, Michigan Integrative Musculoskeletal Health Core Center (Overall Application), G859052642, Skeletal stem cell plasticity in craniofacial bone diseases.
OpenAlex ID: W4410850609