Does cartilage ERα overexpression correlate with osteoarthritic chondrosenescence? Indications from Labisia pumila OA mitigation
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Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into non-treated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 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 cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers’ (matrix metalloproteinase (MMP)-13, RUNX2, COL10α, ERα, CASP3 and HIF-2α) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP 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 cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ERα over-expression showed a strong positive correlation with MMP-13, COL10α1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.
KeywordsERα diclofenac Labisia pumila osteoarthritis subchondral bone
We acknowledge the Ministry of Agriculture, Herbal Development Division for the research grant, Universiti Malaysia Perlis for the studentship, Universiti Putra Malaysia for the facilities and Comparative Medicine and Technology (CoMeT) Unit, Institute of Bioscience, Universiti Putra Malaysia for the assistance in performing all-animal-related procedures. This work was supported by the Herbal Development Division, Ministry of Agriculture, Malaysia (Grant No. NH1014D052).
Compliance with ethical standards
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted; Institutional Animal Care and Use Committee (IACUC), Universiti Putra Malaysia approval (UPM/IACUC/AUP-R050/2015).
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