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Novel role for cyclophilin A in regulation of chondrogenic commitment and endochondral ossification.
Guo, Mian; Shen, Jia; Kwak, Jin Hee; Choi, Bogyu; Lee, Min; Hu, Shen; Zhang, Xinli; Ting, Kang; Soo, Chia B; Chiu, Robert H.
Afiliação
  • Guo M; Dental and Craniofacial Research Institute and Division of Oral Biology, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Shen J; Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Kwak JH; Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Choi B; Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Lee M; Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Hu S; Dental and Craniofacial Research Institute and Division of Oral Biology, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Zhang X; Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Ting K; Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
  • Soo CB; Department of Orthopedic Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, California, USA Division of Plastic and Reconstructive Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • Chiu RH; Dental and Craniofacial Research Institute and Division of Oral Biology, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA Jonsson Comprehensive Cancer Center and Division of Surgical Oncology, School of Medicine, University of California, Los Angeles, Los Ange
Mol Cell Biol ; 35(12): 2119-30, 2015 Jun.
Article em En | MEDLINE | ID: mdl-25870110
Recent studies showed that cyclophilin A (CypA) promotes NF-κB/p65 nuclear translocation, resulting in enhanced NF-κB activity and altered expression of its target genes, such as the Sox9 transcriptional factor, which plays a critical role in chondrogenic differentiation and endochondral ossification. In this report, we unveil the role of CypA in signal-induced chondrogenic differentiation and endochondral ossification. Expression levels of the chondrogenic differentiation markers and transcriptional regulators Sox9 and Runx2 were all significantly lower in CypA knockdown chondrogenic cells than in wild-type cells, indicating that CypA plays a functional role in chondrogenic differentiation. In vitro differentiation studies using micromass cultures of mouse limb bud cells further supported the conclusion that CypA is needed for chondrogenic differentiation. Newborn CypA-deficient pups double stained with alcian blue and alizarin red exhibited generalized, pronounced skeletal defects, while high-resolution micro-computed tomography (microCT) analyses of the femurs and lumbar vertebrae revealed delayed or incomplete endochondral ossification. Comparative histology and immunohistochemistry (IHC) analyses further verified the effects of CypA deficiency on chondrogenic differentiation. Our results provide evidence for the important contribution of CypA as a pertinent component acting through NF-κB-Sox9 in regulation of chondrogenesis signaling. These findings are important to better understand signal-induced chondrogenesis of chondrogenic progenitors in physiological and pathophysiological contexts.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Condrogênese / Ciclofilina A Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Condrogênese / Ciclofilina A Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos