Exercise induced meteorin-like protects chondrocytes against inflammation and pyroptosis in osteoarthritis by inhibiting PI3K/Akt/NF-κB and NLRP3/caspase-1/GSDMD signaling

Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets

“…This postulation was also based on the observed negative association between SF-metrnl and MMP-13 which is a well-known degradative marker during OA pathogenesis [ 131 , 155 ]. In agreement with our results, a recently published article has reported an association between the increasing level of metrnl and the alleviation of OA severity [ 132 ]. Liu and co-workers referred metrnl’s anti-inflammatory effect to the suppression of the PI3K (Phosphoinositide-3-kinases)/Akt/NF-κB pathway.…”

“… • Reduces chondrocyte pyroptosis by blocking the NLRP-3/caspase-1/GSDMD cascade. Sobieh et al [ 131 ] Liu et al [ 132 ] Retinol Binding Protein 4 (RBP4) • Positive association was recorded between its level and MMP-1 and MMP-3. Scotece et al [ 133 ] JAK/STAT3: Janus kinase/signal transducer and activator of transcription protein-3, mTOR: the mammalian target of rapamycin, ROS: reactive oxygen species MMP: matrix metalloproteinase, ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs, JNK: c-Jun N-terminal kinases, MAPK: mitogen activated protein kinase, NF-κB: nuclear factor-kappa B, NO: nitric oxide, IL: interleukin, PGE2: prostaglandin E2, LOXL3: Lysyl oxidase-like 3, CCL: C–C motif chemokine ligand, TLR4: toll-like receptor 4, Akt: protein kinase B, ERK: extracellular signal-regulated kinase, CAP1: adenylyl cyclase-associated protein 1, C/EBP-β: C/enhancer binding protein β, TNF-α: tumor necrosis factor α, CCL3L1: CCL3 like 1, CXCL: C-X-C motif chemokine ligand, CX3CL1: C-X3-C motif chemokine ligand 1, COX-2: cyclooxygenase-2, PI3K: Phosphoinositide-3-kinases, AP-1: activator protein 1, miR: micro-RNA, TIMP-2: tissue inhibitor matrix metalloproteinase 2, AMPK: adenosine monophosphate-activated protein kinase, LPS: lipopolysaccharide, TNFR: tumor necrosis factor receptor, RANKL: receptor activator of NF-κB ligand, LXRα: liver X receptor α, PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1α, SF: synovial fluid, NLRP-3: nod-like receptor protein-3 and GSDMD: gasdermin D. …”

“…This was associated by increasing in the expression of collagen II and inhibiting the expression of MMP-13 and ADAMTS-5. In the same study, metrnl reduced chondrocyte pyroptosis (the inflammatory form of programmed cell death) by blocking the nod-like receptor protein-3/caspase-1/gasdermin D cascade [ 132 ]. Collectively, these findings portray metrnl as a potential novel therapeutic target for OA and open the door for future research to further elucidate its mechanism of action in obesity-OA interplay [ 131 ].…”

“…It was reported that RBP4 impairs insulin signalling pathways either via the activation of PI3K/Akt or the activation of JAK2 (Janus kinase 2)/STAT5 [ 157 , 162 ]. It is noteworthy that the activation of PI3K/Akt or JAK signalling stimulates inflammation, catabolism and apoptosis in OA [ 97 , 109 , 129 , 132 ].…”

PPARγ controls ESCRT-dependent fibroblast-like synoviocyte exosome biogenesis and Alleviates Chondrocyte Osteoarthritis Mediated by Exosomal ANXA1

“…Current clinical guidelines widely recommend non-surgical therapies like physical exercise as first-line treatments [8]. Our prior research has established a moderate treadmill exercise protocol and demonstrated its beneficial effects in ameliorating OA [9][10][11][12][13]. We further identified the potential role of peroxisome proliferator-activated receptor γ (PPARγ), a common upstream element in our sequential studies on irisin [9] and Meteorin-like (metrnl) [10] in OA exercise therapy.…”