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Research Paper|Volume 10, Issue 12|pp 4152—4165

Mechanistic insight into hyaluronic acid and platelet-rich plasma-mediated anti-inflammatory and anti-apoptotic activities in osteoarthritic mice

Chi-Sheng Chiou1,2, Chi-Ming Wu3, Navneet Kumar Dubey4,5, Wen-Cheng Lo6,7, Feng-Chou Tsai8, Tran Dang Xuan Tung1,9, Wei-Ching Hung10, Wei-Che Hsu10, Wei-Hong Chen10, Win-Ping Deng1,10,11
  • 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
  • 2Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
  • 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
  • 4Ceramics and Biomaterials Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam
  • 5Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam
  • 6School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 7Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan
  • 8School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
  • 9Stem Cells Center, Van Hanh General Hospital, Ho Chi Minh City, Vietnam
  • 10Stem Cell Research Center, College of Oral Medicine, , Taiwan
  • 11Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan
Received: August 24, 2018Accepted: December 6, 2018Published: December 23, 2018
https://doi.org/10.18632/aging.101713

Copyright: © 2018 Chiou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) poses a major clinical challenges owing to limited regenerative ability of diseased or traumatized chondrocytes in articular cartilage. Previous studies have determined the individual therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) on OA; however, the underlying mechanism is still lacking. Therefore, we investigated mechanistic approach of HA+PRP therapy on chondrocyte apoptosis in IL-1β+TNF-α (I+T) treated in vitro OA model, in addition to in vivo anterior cruciate ligament transection-OA mice model. MTT assay showed an enhanced chondrocyte proliferation and viability in HA+PRP-treated group, compared to I+T, I+T/HA, I+T/PRP, I+T/HA+PRP groups. Further, HA+PRP also significantly suppressed ROS, apoptotic cleaved caspase-3 and PARP, p53 and p21 and MMP-1; whereas, cell cycle modulatory proteins including p-ERK, cyclin B1, D1, and E2 were upregulated. The sub-G1 population and TUNEL assay confirmed the higher abundance of healthy chondrocytes in HA+PRP group. A significantly decreased ARS staining in HA+PRP group was also noted, indicating reduced cartilaginous matrix mineralization compared to other groups. Conclusively, compared to HA or PRP, the combined HA+PRP might be a promising therapy for articular cartilage regeneration in osteoarthritic pathology, possibly via augmented anti-inflammatory, anti-oxidative chondrocyte proliferation and inhibited MMP-1 activity and matrix calcification.