DOI: 10.1101/gad.1224204. Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes

Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes

10.1101/gad.1224204

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth plate and impaired bone healing with abnormal accumulation of postmitotic but nonhypertrophic chondrocytes. Ex vivo culture of KMI chondrocytes reproduced the differentiation impairment, which was restored by introducing the adenovirus-mediated cGKII gene. The expression of Sox9, an inhibitory regulator of hypertrophic differentiation, persisted in the nuclei of postmitotic chondrocytes of the KMI growth plate. Transfection experiments in culture systems revealed that cGKII attenuated the Sox9 functions to induce the chondrogenic differentiation and to inhibit the hypertrophic differentiation of chondrocytes. This attenuation of Sox9 was due to the cGKII inhibition of nuclear entry of Sox9. The impaired differentiation of cultured KMI chondrocytes was restored by the silencing of Sox9 through RNA interference. Hence, the present study for the first time shed light on a novel role of cGKII as a molecular switch, coupling the cessation of proliferation and the start of hypertrophic differentiation of chondrocytes through attenuation of Sox9 function.

Bibliography

Chikuda, H., Kugimiya, F., Hoshi, K., Ikeda, T., Ogasawara, T., Shimoaka, T., Kawano, H., Kamekura, S., Tsuchida, A., Yokoi, N., Nakamura, K., Komeda, K., Chung, U., & Kawaguchi, H. (2004). Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes. Genes & Development, 18(19), 2418â2429.

Authors 14

Hirotaka Chikuda (first)
Fumitaka Kugimiya (additional)
Kazuto Hoshi (additional)
Toshiyuki Ikeda (additional)
Toru Ogasawara (additional)
Takashi Shimoaka (additional)
Hirotaka Kawano (additional)
Satoru Kamekura (additional)
Atsuko Tsuchida (additional)
Norihide Yokoi (additional)
Kozo Nakamura (additional)
Kajuro Komeda (additional)
Ung-il Chung (additional)
Hiroshi Kawaguchi (additional)

References 36 Referenced 111

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Dates

Type	When
Created	20 years, 11 months ago (Oct. 4, 2004, 2:22 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 11:15 p.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:22 a.m.)
Issued	20 years, 11 months ago (Oct. 1, 2004)
Published	20 years, 11 months ago (Oct. 1, 2004)
Published Online	20 years, 11 months ago (Oct. 1, 2004)
Published Print	20 years, 11 months ago (Oct. 1, 2004)

Funders 0

None

BibTeX

@article{Chikuda_2004, title={Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes}, volume={18}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1224204}, DOI={10.1101/gad.1224204}, number={19}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Chikuda, Hirotaka and Kugimiya, Fumitaka and Hoshi, Kazuto and Ikeda, Toshiyuki and Ogasawara, Toru and Shimoaka, Takashi and Kawano, Hirotaka and Kamekura, Satoru and Tsuchida, Atsuko and Yokoi, Norihide and Nakamura, Kozo and Komeda, Kajuro and Chung, Ung-il and Kawaguchi, Hiroshi}, year={2004}, month=oct, pages={2418–2429} }

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