Defining matrix Gla protein expression in the Dunkin-Hartley guinea pig model of spontaneous osteoarthritis

Abstract

Background Matrix 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. Method Twenty-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. Results The 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). Conclusion Increased 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.

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…The pathogenesis of OA has not yet been fully elucidated, as it is a multifactorial process. Previous studies of our research team mainly focused on protein-coding genes in OA [ 147 , 148 ]; however, we found that recent studies on its pathogenesis have shifted focus to the roles of noncoding RNAs by literature search. Therefore, we summarized the lncRNAs that play a role in osteoarthritic cartilage in this review.…”

Naturally Occurring Osteoarthritis Features and Treatments: Systematic Review on the Aged Guinea Pig Model

“…At 12 months, the surface was eroded until complete cartilage loss at 15 months [16][17][18][19]. OARSI and Mankin scores worsened with aging, as well as CT, instantaneous modulus, cellularity, matrix integrity, insulin growth factor 1 (IGF1), and receptor activator of nuclear factor kappa-B ligand (RANKL) [20][21][22][23]. During aging, as regards SB, an increase in Tb.Th and osteoprotegerin (OPG) and a decrease in bone volume/tissue volume (BV/TV), trabecular bone pattern factor (Tb.Pf), and structure model index (SMI) were observed [17,18,20].…”