Research Paper Volume 11, Issue 9 pp 2797—2811
Chondroprotective effects of platelet lysate towards monoiodoacetate-induced arthritis by suppression of TNF-α-induced activation of NF-ĸB pathway in chondrocytes
- 1 The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
- 2 Center for Stem Cell Translational Research, Zhejiang Chinese Medical University, Hangzhou, China
- 3 Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- 4 College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
- 5 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
received: December 15, 2018 ; accepted: May 2, 2019 ; published: May 14, 2019 ;https://doi.org/10.18632/aging.101952
How to Cite
Copyright: Yan 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.
Platelet lysate (PL) contains a cocktail of growth factors that actively participates in cartilage repair. This study was designed to determine the effect and mechanism of PL on osteoarthritis (OA). An arthritis model was established to mimic human OA by intra-articular injection of monoiodoacetate (MIA) to Sprague Dawley (SD) rats. The model was weekly treated with PL by intra-articular injection. Thermal withdrawal latency, mechanical withdrawal threshold, and treadmill gait were tested for pain behavior observation. Histopathological and immunohistochemical analyses were conducted for evaluating cartilage degradation. Real time PCRs and Western blots were conducted to elucidate the mechanism of PL on primary chondrocytes. Results showed that, in vivo, PL significantly attenuated pain symptoms and exerted chondrocyte-protective and extracellular matrix (ECM)-modifying effect on the arthritic cartilage in a dose-dependent manner. The in situ expressions of type II Collagen (Col2) and matrix metalloproteinase 13 (Mmp13) in the arthritic cartilage was abnormal and was restored by PL. In vitro, PL significantly restored tumor necrosis factor α (TNF-α)-suppressed anabolic gene expression (Col2 and aggrecan) and TNF-α-increased catabolic gene expression (Col10, Mmp13, Adamts5, and Adamts9) in chondrocytes. The effects were mediated by TNF-α downstream signaling, including inhibition of NF-κB and c-Jun activities. This study provides certain knowledge of anti-OA effect and TNF signaling-related mechanism of PL, placing it as a promising and alternative option for OA therapy in the future.
ABH: alcian blue hematoxylin; AP-1: activator protein 1; Col2: collagen II; ECM: extracellular matrix; EGF: epidermal growth factor; HE: hematoloxylin-eosin; IGF: insulin-like growth factor; IKK: inhibitory κB kinase; IL-1: interleukin-1; IMDM: Iscove's modified Dulbecco's medium; JNK: c-Jun N-terminal kinase; KOOS: Knee Osteoarthritis and Disability Outcome Score; LSD: least significant difference; MIA: monoiodoacetate; MMP: matrix metalloproteinase; MWT: mechanical withdrawal threshold; NC: normal control; NF-κB: nuclear factor κB; OA: osteoarthritis; OARSI: Osteoarthritis Research International; Parp: poly (ADP-ribose) polymerase; PBS: phosphate buffered saline; PDGF: platelet derived growth factors; PL: platelyet lysate; PRP: platelet rich plasma; SD: standard deviation; sGAG: sulfated glycosaminoglycan; SO: safranin-O; SD rats: Sprague Dawley rats; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor α; TWL: thermal withdrawal latency; VEGF: vascular endothelial growth factor.