Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification

Chihiro Nakatomi, Mitsushiro Nakatomi, Takuma Matsubara, Toshihisa Komori, Takahiro Doi-Inoue, Naozumi Ishimaru, Falk Weih, Tsutomu Iwamoto, Miho Matsuda, Shoichiro Kokabu, Eijiro Jimi

研究成果: ジャーナルへの寄稿記事

抄録

Endochondral ossification is important for skeletal development. Recent findings indicate that the p65 (RelA) subunit, a main subunit of the classical nuclear factor-κB (NF-κB) pathway, plays essential roles in chondrocyte differentiation. Although several groups have reported that the alternative NF-κB pathway also regulates bone homeostasis, the role of the alternative NF-κB 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-κB pathway may regulate chondrocyte proliferation and differentiation to maintain endochondral ossification.

元の言語英語
ページ(範囲)29-41
ページ数13
ジャーナルBone
121
DOI
出版物ステータス出版済み - 4 1 2019

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Chondrocytes
Osteogenesis
Collagen Type X
Ankyrin Repeat
Matrix Metalloproteinase 13
Aggrecans
Dwarfism
Growth Plate
Terminal Repeat Sequences
Bromodeoxyuridine
Homeostasis
Bone and Bones
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

これを引用

Nakatomi, C., Nakatomi, M., Matsubara, T., Komori, T., Doi-Inoue, T., Ishimaru, N., ... Jimi, E. (2019). Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification. Bone, 121, 29-41. https://doi.org/10.1016/j.bone.2019.01.002

Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification. / Nakatomi, Chihiro; Nakatomi, Mitsushiro; Matsubara, Takuma; Komori, Toshihisa; Doi-Inoue, Takahiro; Ishimaru, Naozumi; Weih, Falk; Iwamoto, Tsutomu; Matsuda, Miho; Kokabu, Shoichiro; Jimi, Eijiro.

:: Bone, 巻 121, 01.04.2019, p. 29-41.

研究成果: ジャーナルへの寄稿記事

Nakatomi, C, Nakatomi, M, Matsubara, T, Komori, T, Doi-Inoue, T, Ishimaru, N, Weih, F, Iwamoto, T, Matsuda, M, Kokabu, S & Jimi, E 2019, 'Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification', Bone, 巻. 121, pp. 29-41. https://doi.org/10.1016/j.bone.2019.01.002
Nakatomi C, Nakatomi M, Matsubara T, Komori T, Doi-Inoue T, Ishimaru N その他. Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification. Bone. 2019 4 1;121:29-41. https://doi.org/10.1016/j.bone.2019.01.002
Nakatomi, Chihiro ; Nakatomi, Mitsushiro ; Matsubara, Takuma ; Komori, Toshihisa ; Doi-Inoue, Takahiro ; Ishimaru, Naozumi ; Weih, Falk ; Iwamoto, Tsutomu ; Matsuda, Miho ; Kokabu, Shoichiro ; Jimi, Eijiro. / Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification. :: Bone. 2019 ; 巻 121. pp. 29-41.
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abstract = "Endochondral ossification is important for skeletal development. Recent findings indicate that the p65 (RelA) subunit, a main subunit of the classical nuclear factor-κB (NF-κB) pathway, plays essential roles in chondrocyte differentiation. Although several groups have reported that the alternative NF-κB pathway also regulates bone homeostasis, the role of the alternative NF-κB 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-κB pathway may regulate chondrocyte proliferation and differentiation to maintain endochondral ossification.",
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AU - Doi-Inoue, Takahiro

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