Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage

Harumi Kawaki, Satoshi Kubota, Akiko Suzuki, Noureddine Lazar, Tomohiro Yamada, Tatsushi Matsumura, Toshihiro Ohgawara, Takeyasu Maeda, Bernard Perbal, Karen M. Lyons, Masaharu Takigawa

研究成果: ジャーナルへの寄稿記事

83 引用 (Scopus)

抄録

CCN2 is best known as a promoter of chondrocyte differentiation among the CCN family members, and its null mice display skeletal dysmorphisms. However, little is known concerning roles of the other CCN members in chondrocytes. Using both in vivo and in vitro approaches, we conducted a comparative analysis of CCN2-null and wildtype mice to study the roles of CCN2 and the other CCN proteins in cartilage development. Immunohistochemistry was used to evaluate the localization of CCN proteins and other chondrocyte-associated molecules in the two types of mice. Moreover, gene expression levels and the effects of exogenous CCN proteins on chondrocyte proliferation, differentiation, and the expression of chondrocyte-associated genes in their primary chondrocytes were evaluated. Ccn3 was dramatically upregulated in CCN2-null cartilage and chondrocytes. This upregulation was associated with diminished cell proliferation and delayed differentiation. Consistent with the in vivo findings, CCN2 deletion entirely retarded chondrocyte terminal differentiation and decreased the expression of several chondrocyte-associated genes in vitro, whereas Ccn3 expression drastically increased. In contrast, the addition of exogenous CCN2 promoted differentiation strongly and induced the expression of the associated genes, whereas decreasing the Ccn3 expression. These findings collectively indicate that CCN2 induces chondrocyte differentiation by regulating the expression of chondrocyte-associated genes but that these effects are counteracted by CCN3. The lack of CCN2 caused upregulation of CCN3 in CCN2-null mice, which resulted in the observed phenotypes, such as the resultant delay of terminal differentiation. The involvement of the PTHrP-Ihh loop in the regulation of CCN3 expression is also suggested.

元の言語英語
ページ(範囲)1751-1764
ページ数14
ジャーナルJournal of Bone and Mineral Research
23
発行部数11
DOI
出版物ステータス出版済み - 11 1 2008
外部発表Yes

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CCN Intercellular Signaling Proteins
Chondrocytes
Cartilage
Up-Regulation
Genes
Gene Expression
Parathyroid Hormone-Related Protein
Proteins

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

これを引用

Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. / Kawaki, Harumi; Kubota, Satoshi; Suzuki, Akiko; Lazar, Noureddine; Yamada, Tomohiro; Matsumura, Tatsushi; Ohgawara, Toshihiro; Maeda, Takeyasu; Perbal, Bernard; Lyons, Karen M.; Takigawa, Masaharu.

:: Journal of Bone and Mineral Research, 巻 23, 番号 11, 01.11.2008, p. 1751-1764.

研究成果: ジャーナルへの寄稿記事

Kawaki, H, Kubota, S, Suzuki, A, Lazar, N, Yamada, T, Matsumura, T, Ohgawara, T, Maeda, T, Perbal, B, Lyons, KM & Takigawa, M 2008, 'Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage', Journal of Bone and Mineral Research, 巻. 23, 番号 11, pp. 1751-1764. https://doi.org/10.1359/jbmr.080615
Kawaki, Harumi ; Kubota, Satoshi ; Suzuki, Akiko ; Lazar, Noureddine ; Yamada, Tomohiro ; Matsumura, Tatsushi ; Ohgawara, Toshihiro ; Maeda, Takeyasu ; Perbal, Bernard ; Lyons, Karen M. ; Takigawa, Masaharu. / Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. :: Journal of Bone and Mineral Research. 2008 ; 巻 23, 番号 11. pp. 1751-1764.
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AU - Kawaki, Harumi

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AU - Suzuki, Akiko

AU - Lazar, Noureddine

AU - Yamada, Tomohiro

AU - Matsumura, Tatsushi

AU - Ohgawara, Toshihiro

AU - Maeda, Takeyasu

AU - Perbal, Bernard

AU - Lyons, Karen M.

AU - Takigawa, Masaharu

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