| First Author | Nakatomi C | Year | 2019 |
| Journal | Bone | Volume | 121 |
| Pages | 29-41 | PubMed ID | 30611922 |
| Mgi Jnum | J:273256 | Mgi Id | MGI:6286766 |
| Doi | 10.1016/j.bone.2019.01.002 | Citation | Nakatomi C, et al. (2019) Constitutive activation of the alternative NF-kappaB pathway disturbs endochondral ossification. Bone 121:29-41 |
| abstractText | Endochondral ossification is important for skeletal development. Recent findings indicate that the p65 (RelA) subunit, a main subunit of the classical nuclear factor-kappaB (NF-kappaB) pathway, plays essential roles in chondrocyte differentiation. Although several groups have reported that the alternative NF-kappaB pathway also regulates bone homeostasis, the role of the alternative NF-kappaB pathway in chondrocyte development is still unclear. Here, we analyzed the in vivo function of the alternative pathway on endochondral ossification using p100-deficient (p100(-/-)) mice, which carry a homozygous deletion of the COOH-terminal ankyrin repeats of p100 but still express functional p52 protein. The alternative pathway was activated during the periarticular stage in wild-type mice. p100(-/-) mice exhibited dwarfism, and histological analysis of the growth plate revealed abnormal arrangement of chondrocyte columns and a narrowed hypertrophic zone. Consistent with these observations, the expression of hypertrophic chondrocyte markers, type X collagen (ColX) or matrix metalloproteinase 13, but not early chondrogenic markers, such as Col II or aggrecan, was suppressed in p100(-/-) mice. An in vivo BrdU tracing assay clearly demonstrated less proliferative activity in chondrocytes in p100(-/-) mice. These defects were partly rescued when the RelB gene was deleted in p100(-/-) mice. Taken together, the alternative NF-kappaB pathway may regulate chondrocyte proliferation and differentiation to maintain endochondral ossification. |
