Abstract
BackgroundMatrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model.MethodTwenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage.ResultsThe histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05).ConclusionIncreased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.
Highlights
Osteoarthritis (OA) is the most common degenerative joint disease of the middle-aged and elderly [1]
Increased expression of Matrix Gla (γ-carboxyglutamate) protein (MGP) in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity
MGP was reported as an anti-inflammation cytokine, may have the effects of alleviating inflammatory reaction in patients with acute pancreatitis and arthritis [7, 8]. rs1800802 located in an MGP polymorphic site has been reported in association with an increased OA risk in a Han Chinese population [9, 10]
Summary
Osteoarthritis (OA) is the most common degenerative joint disease of the middle-aged and elderly [1]. Ma et al BMC Musculoskelet Disord (2021) 22:870 research focus, but biomarkers of OA severity are rarely reported. MGP may function as an inhibitor of ectopic calcification in cardiovascular tissues and cartilage, but the detailed mechanism remains unclear. MGP has been shown to inhibit BMP-2-induced calcification and spontaneous vascular calcification [5], and MGP mutation may lead to Keutel syndrome, a genetic disorder that is mainly characterized by multiple pathological changes including cartilage calcification, brachydactyly, and pulmonary artery stenosis [6]. A potential association between MGP and OA has been suggested, there is still no consensus or detailed mechanism regarding the presence and effect of MGP in OA severity and natural history. Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model
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