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• W4302757232 abstract "Abstract Background: Intra-articular injection of monoiodoacetate (MIA) has shown to induce extensive chondrocyte degeneration/death in articular cartilage (AC), resulting in destruction of the AC in animals. This has been used often as model of osteoarthritis (OA). Pigment epithelium-derived factor (PEDF) and its derived short peptide 29-mer have been shown to heal tissue injury by activating various types of stem/progenitor cells localized near the lesions. Here we investigated whether the 29-mer is able to evoke chondrogenesis in rats with MIA-injured AC. Methods: AC destruction was induced in Sprague-Dawley rats by a single intra-articular injection of MIA (1 mg) in the right knee. After MIA injection for 7 days, the 29-mer infused with 5% hyaluronic acid (HA) was injected intra-articularly twice, at 4-day intervals. Also, BrdU was injected intraperitoneally into the rats to detect cell proliferation in the damaged AC. The histopathology of AC was determined by hematoxylin and eosin (H&E) staining and Safranin O staining. The regeneration of chondrocytes in the AC was detected by dual-immunostaining of BrdU and chondrocyte markers, including aggrecan, collagen type 2 and Sox9. Changes in hind paw weight distribution were measured to evaluate the MIA-induced joint discomfort. Bone marrow-derived mesenchymal stem cells (MSCs) were used to detect chondrogenic differentiation. The involvement of the PEDF receptor and STAT3 signaling on the 29-mer effects was evaluated using specific inhibitors. Results: MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC, accompanied by the partial recovery of the cartilaginous matrix. The 29-mer/HA also exerted an antinociceptive effect in rats. In culture, the 29-mer promoted chondrogenic differentiation of MSCs with evidence of increased expression of chondrogenic marker genes and proteoglycans, as well as the phosphorylation of STAT3. Pharmacological inhibitors of PEDF-R and STAT3 signaling dramatically blocked the 29-mer effects on cultured MSCs and chondrogenesis in the injured AC. Conclusions: The 29-mer/HA formulation has the ability to stimulate chondrocyte regeneration in the MIA damaged AC. The 29-mer may be a novel agent for the development of future OA treatments." @default.
• W4302757232 created "2022-10-07" @default.
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• W4302757232 date "2022-10-06" @default.
• W4302757232 modified "2023-09-27" @default.
• W4302757232 title "PEDF peptide stimulates chondrocyte regeneration in rats with monoiodoacetate-induced articular cartilage injury" @default.
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• W4302757232 doi "https://doi.org/10.21203/rs.3.rs-2128208/v1" @default.
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