title: Novel role for cyclophilin A in regulation of chondrogenic commitment and endochondral ossification.
abstract: 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.
authors: 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.
authors: Mian
authors: M
authors: Guo
authors: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Jia
authors: J
authors: Shen
authors: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Jin Hee
authors: JH
authors: Kwak
authors: Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Bogyu
authors: B
authors: Choi
authors: Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Min
authors: M
authors: Lee
authors: Dental and Craniofacial Research Institute and Division of Oral Biology, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Shen
authors: S
authors: Hu
authors: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Xinli
authors: X
authors: Zhang
authors: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
authors: Kang
authors: K
authors: Ting
authors: 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.
authors: Chia B
authors: CB
authors: Soo
authors: 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 Angeles, California, USA rchiu@dentistry.ucla.edu.
authors: Robert H
authors: RH
authors: Chiu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D021984:Cyclophilin A / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis; D055114:X-Ray Microtomography
chemical_list: D016328:NF-kappa B; D021984:Cyclophilin A