ABSTRACT
Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed aftertreatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterallyovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX?OA control, OVX?OA ? diclofenac (5 mg/kg) (positive control), OVX?OA ? LP leaf extract (150 and300 mg/kg) and healthy sham control. After 8 weeks’ treatment, their conditions were evaluated via serum biomarkers,knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilageerosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenacand the non-treated OA. The cartilage catabolic markers’ (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa,CASP3 and HIF-2a) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased byLP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilageprotective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondralbone restoration. The cartilage ERa over-expression showed a strong positive correlation with MMP-13, COL10a1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.