The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signa...The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks.Plagl1,which encodes a zinc finger transcription factor,is a paternally expressed gene.We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell(CNCC)-derived lineage cells in mouse condyles.Using the CNCC-derived lineage-specific Plagl1 knockout mouse model,we evaluate the function of PLAGL1 during postnatal mouse condyle development.Our findings show that PLAGL1 contributes significantly to osteoblast differentiation,and its deficiency impairs osteogenic lineage differentiation,which consequently disrupts mandibular condyle development.Mechanistically,insulin-like growth factor 2(IGF2)in complex with IGF-binding proteins(IGFBPs)has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis.Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway,leading to disordered glucose metabolism,defective extracellular matrix organization,and impaired ossification.Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency.In conclusion,the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.展开更多
基金sponsored by funding from the National Natural Science Foundation of China(82201004 to J.D.,81921002 to X.J.,82130027 to X.J.)the Young Elite Scientists Sponsorship Program by CAST(YESS20230102 to J.D.)the innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20212400 to X.J.).
文摘The mandibular condyle is a critical growth center in craniofacial bone development,especially during postnatal stages.Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks.Plagl1,which encodes a zinc finger transcription factor,is a paternally expressed gene.We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell(CNCC)-derived lineage cells in mouse condyles.Using the CNCC-derived lineage-specific Plagl1 knockout mouse model,we evaluate the function of PLAGL1 during postnatal mouse condyle development.Our findings show that PLAGL1 contributes significantly to osteoblast differentiation,and its deficiency impairs osteogenic lineage differentiation,which consequently disrupts mandibular condyle development.Mechanistically,insulin-like growth factor 2(IGF2)in complex with IGF-binding proteins(IGFBPs)has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis.Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway,leading to disordered glucose metabolism,defective extracellular matrix organization,and impaired ossification.Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency.In conclusion,the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
