| Title | RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells |
| Authors | Zhang, Shuai Hamid, Md Rana Wang, Ting Liao, Jinqi Wen, Liru Zhou, Yan Wei, Pengfei Zou, Xuenong Chen, Gang Chen, Junhui Zhou, Guangqian |
| Affiliation | Shenzhen Univ, Dept Med Cell Biol & Genet, Guangdong Key Lab Genom Stabil & Dis Prevent, Shenzhen Key Lab Antiaging & Regenerat Med, Shenzhen 518060, Peoples R China Shenzhen Univ, Hlth Sci Ctr, Shenzhen Engn Lab Regenerat Technol Orthopaed Dis, Shenzhen 518060, Peoples R China Lungene Technol, B606,Yinxing Sci Bldg, Shenzhen 510086, Peoples R China Shenzhen Univ, Gen Hosp, Dept Internal Med, Shenzhen 518060, Peoples R China Sun Yat Sen Univ, Affiliated Hosp 1, Dept Spine Surg, Orthoped Res Inst,Guangdong Prov Key Lab Orthoped, Guangzhou 510080, Peoples R China Nanchang Univ, Jiangxi Prov Peoples Hosptial, Nanchang 330006, Jiangxi, Peoples R China Peking Univ, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Shenzhen Hosp, Intervent & Cell Therapy Ctr, Shenzhen 518035, Guangdong, Peoples R China |
| Keywords | DEGENERATIVE JOINT DISEASE MESENCHYMAL STEM-CELLS SPONTANEOUS OSTEOARTHRITIS ARTICULAR-CARTILAGE STR/ORT MOUSE REPAIR MODEL PHOSPHORYLATION IDENTIFICATION LOCALIZATION |
| Issue Date | 2020 |
| Publisher | THERANOSTICS |
| 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>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>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. |
| URI | http://hdl.handle.net/20.500.11897/591904 |
| ISSN | 1838-7640 |
| DOI | 10.7150/thno.44875 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
