Rps6ka2 enhances iMSC chondrogenic differentiation to attenuate knee osteoarthritis through articular cartilage regeneration in mice

  • Biochem Biophys Res Commun. 2023 Jun 30:663:61-70. doi: 10.1016/j.bbrc.2023.04.049.
Juan Zhang  1 ,  Jin-Qi Liao  2 ,  Li-Ru Wen  3 ,  Arshad-Ahmed Padhiar  4 ,  Zhu Li  5 ,  Zhong-Yuan He  6 ,  Hua-Chuan Wu  7 ,  Jian-Feng Li  8 ,  Shuai Zhang  9 ,  Yan Zhou  10 ,  Xiao-Hua Pan  11 ,  Jian-Hua Yang  12 ,  Guang-Qian Zhou  13
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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China; The Affiliated Nanhua Hospital, Department of Endocrinology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: [email protected].
  • 2. Lungene Biotech Ltd., Longhua District, Shenzhen, 518107, China. Electronic address: [email protected].
  • 3. 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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 4. 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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 5. 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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 6. Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 7. Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 8. Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: [email protected].
  • 9. Brain Research Centre and Department of Biology, Southern University of Science and Technology, Shenzhen, 518107, China. Electronic address: [email protected].
  • 10. 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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China; Lungene Biotech Ltd., Longhua District, Shenzhen, 518107, China. Electronic address: [email protected].
  • 11. Department of Orthopaedics, The Second Affiliated Hospital of Shenzhen University, The Second School of Clinical Medicine, Southern Medical University, The Clinical Medical College of Guangdong Medical University, People's Hospital of Shenzhen Baoan District, Shenzhen, 518107, China. Electronic address: [email protected].
  • 12. The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 518107, China. Electronic address: [email protected].
  • 13. 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, Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, 518107, China. Electronic address: [email protected].
PMID: 37119767 DOI: 10.1016/j.bbrc.2023.04.049
Abstract

Articular cartilage (AC) is most susceptible to degeneration in knee Osteoarthritis (OA); however, the existing treatments for OA do not target the core link of the pathogenesis-"decreased tissue cell function activity and extracellular matrix (ECM) metabolic disorders" for effective intervention. iMSC hold lower heterogeneity and great promise in biological research and clinical applications. Rps6ka2 may play an important role in the iMSC to treat OA. In this study, the CRISPR/Cas9 Gene Editing Rps6ka2-/- iMSC were obtained. Effect of Rps6ka2 on iMSC proliferation and chondrogenic differentiation was evaluated in vitro. An OA model was constructed in mice by surgical destabilization of medial meniscus (DMM). The Rps6ka2-/- iMSC and iMSC were injected into the articular cavity twice-weekly for 8 weeks. In vitro experiments showed that Rps6ka2 could promote iMSC proliferation and chondrogenic differentiation. In vivo results further confirmed that Rps6ka2 could improve iMSC viability to promote ECM production to attenuate OA in mice.

Keywords
Articular cartilage regeneration; Chondrogenic differentiation; Knee osteoarthritis; Rps6ka2; iMSC.
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