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

Chi-Sheng Chiou,Chi-Ming Wu,Wen-Cheng Lo,Win-Ping Deng,Tran Dang Xuan Tung,Wei-Ching Hung,Wei-Che Hsu,Feng-Chou Tsai,Navneet Kumar Dubey,Wei-Hong Chen

doi:10.18632/aging.101713

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.

Highlights

Osteoarthritis (OA) is the debilitating joint condition distinguished by progressive degradation of articular cartilage, leading to stiffness, excessive pain and crepitus
We investigated anti-apoptotic mechanism mediated by hyaluronic acid (HA)+platelet-rich plasma (PRP) in the chondrocytes obtained from osteoarthritic patients
To determine the synergistic effect of HA and PRP (HA+PRP), the cell numbers and extent of viability of chondrocytes were assessed after treatment with IL-1β+ tumor necrosis factor-α (TNF-α) (I+T) for 2 days (Figure 1A)

Summary

Introduction

Osteoarthritis (OA) is the debilitating joint condition distinguished by progressive degradation of articular cartilage, leading to stiffness, excessive pain and crepitus. A growing body of evidence demonstrate that the chondrocyte apoptosis plays a key role in OA physiopathology in which the hyaline articular cartilage covering the articular surfaces undergo mild to severe degradation [2,3,4] This has been attributed to enhanced mechanical and inflammatory stresses; the limited regenerative ability of articular chondrocytes, owing to low mitotic activity renders them highly susceptible to damage leading to reduced ECM deposition and imbalanced knee-joint homeostasis [5, 6]. We simulated the inflammatory osteoarthritic microenvironment in articular chondrocytes by using pro-inflammatory cytokines, the interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which participate in catabolic degradation of ECM proteins

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