title: Bone morphogenetic protein rescues the lack of secondary cartilage in Runx2-deficient mice.
abstract: Secondary cartilages including mandibular condylar cartilage have unique characteristics. They originate from alkaline phosphatase (ALP)-positive progenitor cells of the periosteum, and exhibit characteristic modes of differentiation. They also have a unique extracellular matrix, and coexpress type I, II and X collagens. We have previously shown that there is a total absence of secondary cartilages in Runx2-deficient (Runx2-/-) mice. To clarify whether Runx2 is essential for chondrocytic differentiation of secondary cartilages, we performed an organ culture system using mandibular explants derived from Runx2-/- mice at embryonic day 18.0. Since mRNA for bone morphogenetic protein 2 (BMP2) was strongly expressed in osteoblasts of condylar anlagen in wild-type mice, and was down-regulated in those of Runx2-/- mice, we chose to investigate BMP2 effects on secondary cartilage formation. Condensed mesenchymal cells of mandibular condylar anlagen in precultured explants were ALP-positive and expressed type I collagen and Sox9. After culture with recombinant human (rh) BMP2, chondrocytic cells showing ALP activity and expressing Sox5, Sox9, and type I and II collagens, appeared from mesenchymal condensation. This expression profile was comparable with the reported pattern of chondrocytes in mouse secondary cartilages. However, chondrocyte hypertrophy was not observed in the explants. These findings indicate that BMP2 partially rescued chondrocyte differentiation but not chondrocyte hypertrophy in secondary cartilage formation in Runx2-/- mice. Runx2 is required for chondrocyte hypertrophy in secondary cartilage formation, and it is likely that BMP2, which is abundantly secreted by osteoblasts in condylar anlagen, contributes to the early process of secondary cartilage formation.
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Graduate School, Tokyo Medical and Dental University, Japan. h-fukuoka.mfa@tmd.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fukuoka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shibata
authors.forename: Naoto
authors.initials: N
authors.lastname: Suda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000032:analysis; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology*; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; C493716:Runx2 protein, mouse; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C486344:Six5 protein, mouse; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000469:Alkaline Phosphatase