title: IKKβ in postnatal perichondrium remotely controls endochondral ossification of the growth plate through downregulation of MCP-5.
abstract: IκB kinase β (IKKβ) is a catalytic subunit of the IKK complex, which activates nuclear factor-κB (NF-κB). Although its role in osteoclastogenesis is well established, the role of IKKβ in bone formation is poorly understood. Here, we report that conditional knockout of Ikkβ in limb bud mesenchymal cells results in the upregulation of monocyte chemoattractant protein-5 (MCP-5) in the perichondrium, which in turn inhibits the growth of longitudinal bone by compromising chondrocyte hypertrophy and increasing the apoptosis of chondrocytes within the growth plate. Contrary to expectations, IKKβ in cells of chondrocyte or osteoblast lineage was dispensable for bone growth. On the other hand, ex vivo experiments confirmed the role of MCP-5 in the growth of longitudinal bone. Furthermore, an in vitro study demonstrated that the action of IKKβ on MCP-5 is cell autonomous. Collectively, our results provide evidence for a previously unrecognized role of IKKβ in the regulation of the growth plate that is mediated through stimulation-independent downregulation of MCP-5 in the perichondrium.
authors.affiliation: Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Toguchida
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0723, USA.
authors.forename: M
authors.initials: M
authors.lastname: Karin
authors.affiliation: Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*
chemical_list: C491224:Ccl12 protein, mouse; D018945:Monocyte Chemoattractant Proteins; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse