1. Academic Validation
  2. RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells

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

  • Theranostics. 2020 May 25;10(15):6915-6927. doi: 10.7150/thno.44875.
Shuai Zhang 1 Md Rana Hamid 1 Ting Wang 2 Jinqi Liao 1 Liru Wen 1 Yan Zhou 2 Pengfei Wei 3 Xuenong Zou 4 Gang Chen 5 Junhui Chen 6 Guangqian Zhou 1
Affiliations

Affiliations

  • 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.
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; RSK-3; STR/Ort; osteoarthritis.

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