Theranostics 2020; 10(15):6915-6927. doi:10.7150/thno.44875 This issue Cite

Research Paper

RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells

Shuai Zhang1, Md Rana Hamid1, Ting Wang2, Jinqi Liao1, Liru Wen1, Yan Zhou2, Pengfei Wei3, Xuenong Zou4, Gang Chen5✉, Junhui Chen6✉, Guangqian Zhou1✉

1. Department of Medical Cell Biology and Genetics, Guangdong Key Laboratory of Genomic Stability and Disease Prevention, Shenzhen Key Laboratory of Anti-aging and Regenerative Medicine, and Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Sciences Center, Shenzhen University, Shenzhen 518060, China.
2. Lungene Technologies, B606, Yinxing Scientific Building, Lonhua District, Shenzhen, 510086, China.
3. Department of Internal Medicine, General Hospital of Shenzhen University, Shenzhen University, Shenzhen 518060, China.
4. Department of Spine Surgery, Orthopedic Research Institute, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
5. Jiangxi Provincial People's Hosptial Affiliated to Nanchang University, Nanchang, 330006, Jiangxi, China.
6. Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, Guangdong, China.

Citation:
Zhang S, Hamid MR, Wang T, Liao J, Wen L, Zhou Y, Wei P, Zou X, Chen G, Chen J, Zhou G. RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics 2020; 10(15):6915-6927. doi:10.7150/thno.44875. https://www.thno.org/v10p6915.htm
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Abstract

Graphic abstract

Rationale: Cartilage stem/progenitor cells (CSPC) are a promising cellular source to promote endogenous cartilage regeneration in osteoarthritis (OA). Our previous work indicates that ribosomal s6 kinase 3 (RSK-3) is a target of 4-aminobiphenyl, a chemical enhancing CSPC-mediated cartilage repair in OA. However, the primary function and mechanism of RSK-3 in CSPC-mediated cartilage pathobiology remain undefined.

Methods: We systematically assessed the association of RSK-3 with OA in three mouse strains with varying susceptibility to OA (MRL/MpJ>CBA>STR/Ort), and also RSK-3-/- mice. Bioinformatic analysis was used to identify the possible mechanism of RSK-3 affecting CSPC, which was further verified in OA mice and CSPC with varying RSK-3 expression induced by chemicals or gene modification.

Results: We demonstrated that the level of RSK-3 in cartilage was positively correlated with cartilage repair capacities in three mouse strains (MRL/MpJ>CBA>STR/Ort). Enhanced RSK-3 expression by 4-aminobiphenyl markedly attenuated cartilage injury in OA mice and inhibition or deficiency of RSK-3 expression, on the other hand, significantly aggravated cartilage damage. Transcriptional profiling of CSPC from mice suggested the potential role of RSK-3 in modulating cell proliferation. It was further shown that the in vivo and in vitro manipulation of the RSK-3 expression indeed affected the CSPC proliferation. Mechanistically, ribosomal protein S6 (rpS6) was activated by RSK-3 to accelerate CSPC growth.

Conclusion: RSK-3 is identified as a key regulator to enhance cartilage repair, at least partly by regulating the functionality of the cartilage-resident stem/progenitor cells.

Keywords: Cartilage stem/progenitor cell, MRL/MpJ, osteoarthritis, RSK-3, STR/Ort


Citation styles

APA
Zhang, S., Hamid, M.R., Wang, T., Liao, J., Wen, L., Zhou, Y., Wei, P., Zou, X., Chen, G., Chen, J., Zhou, G. (2020). RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics, 10(15), 6915-6927. https://doi.org/10.7150/thno.44875.

ACS
Zhang, S.; Hamid, M.R.; Wang, T.; Liao, J.; Wen, L.; Zhou, Y.; Wei, P.; Zou, X.; Chen, G.; Chen, J.; Zhou, G. RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics 2020, 10 (15), 6915-6927. DOI: 10.7150/thno.44875.

NLM
Zhang S, Hamid MR, Wang T, Liao J, Wen L, Zhou Y, Wei P, Zou X, Chen G, Chen J, Zhou G. RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics 2020; 10(15):6915-6927. doi:10.7150/thno.44875. https://www.thno.org/v10p6915.htm

CSE
Zhang S, Hamid MR, Wang T, Liao J, Wen L, Zhou Y, Wei P, Zou X, Chen G, Chen J, Zhou G. 2020. RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics. 10(15):6915-6927.

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