Localization and inhibitory effect of basic fibroblast growth factor on chondrogenesis in cultured mouse mandibular condyle.
The condylar cartilage, an important growth site in the mandible, shows characteristic modes of growth and differentiation, unlike the limb bud cartilage. To elucidate the mechanism of chondrogenesis at the condylar cartilage, we analyzed the effects of basic fibroblast growth factor (bFGF) on the growth and development of mouse mandibular condyle using serum-free organ culture and on the expression of genes related to the chondrogenesis. Further, we investigated the localization of bFGF in cultured condyle by immunohistochemistry. The present immunohistochemical observations showed that bFGF is localized in the extracellular matrix of the mesenchymal condylar anlage, the perichondrium and the proliferative cell zone, and that immunostaining was diminished in the metachromatically stained area. In the condyle culture with added recombinant human bFGF (rhbFGF) for 5 days, the area occupied by hypertrophic chondrocytes in the mandibular condylar cartilage was reduced. A reverse transcription-polymerase chain reaction (RT-PCR) assay also showed that the mRNA levels of aggrecan and type X collagen were reduced compared with nontreated tissues. Treatment with rhbFGF for 2 days decreased cell proliferation in the perichondrium, and bFGF downregulated the Indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic protein 4 (BMP4), and core-binding factor alpha1 (Cbfa1) expression in the RT-PCR assay. These findings suggest that bFGF has the ability for inhibitory regulation of condylar growth, via the inhibition of proliferation and differentiation of chondrocytes, and that this inhibitory regulation is related to the downregulation of growth factors and transcription factors.
Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo Japan.
Takuya
T
Ogawa
Hitoyata
H
Shimokawa
Kenji
K
Fukada
Shoichi
S
Suzuki
Shunichi
S
Shibata
Keiichi
K
Ohya
Takayuki
T
Kuroda
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D016895:Culture Media, Serum-Free; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006801:Humans; D008335:Mandibular Condyle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009363:Neoplasm Proteins; D009924:Organ Culture Techniques / Q000379:methods; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D016895:Culture Media, Serum-Free; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2