| First Author | Kobayashi K | Year | 2015 |
| Journal | Cell Death Differ | Volume | 22 |
| Issue | 5 | Pages | 852-61 |
| PubMed ID | 25526093 | Mgi Jnum | J:258900 |
| Mgi Id | MGI:6140696 | Doi | 10.1038/cdd.2014.192 |
| Citation | Kobayashi K, et al. (2015) IKKbeta in postnatal perichondrium remotely controls endochondral ossification of the growth plate through downregulation of MCP-5. Cell Death Differ 22(5):852-61 |
| abstractText | IkappaB kinase beta (IKKbeta) is a catalytic subunit of the IKK complex, which activates nuclear factor-kappaB (NF-kappaB). Although its role in osteoclastogenesis is well established, the role of IKKbeta in bone formation is poorly understood. Here, we report that conditional knockout of Ikkbeta 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, IKKbeta 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 IKKbeta on MCP-5 is cell autonomous. Collectively, our results provide evidence for a previously unrecognized role of IKKbeta in the regulation of the growth plate that is mediated through stimulation-independent downregulation of MCP-5 in the perichondrium. |
