Alendronate protects against articular cartilage erosion by inhibiting subchondral bone loss in ovariectomized rats
ABSTRACT Osteoporosis (OP) and osteoarthritis (OA) are major health problems in the increasing elderly population, particularly in postmenopausal women, but their relationship remains unclear. The present study investigated whether alendronate (ALN), a potent inhibitor of bone resorption, could protect articular cartilage from degeneration in a combined animal model of OP and OA induced by ovariectomy (OVX). Seventy-eight seven-month-old female Sprague-Dawley rats were assigned into five experimental groups: (1) sham-operated with vehicle treatment, (2) sham-operated with ALN treatment, (3) OVX with vehicle treatment, (4) ALN treatment starting at OVX, and (5) ALN treatment starting at eight weeks after OVX. Histological and micro-CT analyses, together with urine collagen degradation markers, indicated that early ALN treatment completely prevented both subchondral bone loss and cartilage surface erosion induced by OVX. Although late ALN treatment also inhibited subchondral bone loss and significantly reduced cartilage erosion in the OVX rats, these tissues did not completely recover even after 10-weeks of ALN treatment. Quantitative RT-PCR analyses showed that the protective effect of ALN correlated with increased ratio of OPG/RANKL in both subchondral bone and cartilage. Moreover, whereas OVX caused upregulation of expression of matrix metalloproteinases MMP-13 and MMP-9 in the articular cartilage and chondrocytes in the interface between the articular cartilage and subchondral bone, respectively, early ALN treatment blocked whereas late ALN treatment attenuated the upregulation of these catabolic enzymes in the corresponding tissues. Together, these data indicate that the subchondral bone loss plays an important role in OA pathogenesis in the combined OP and OA model and suggest that treatment timing is an important factor for the effectiveness of anti-resorptive drugs therapy of combined OP and OA.
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ABSTRACT: Temporomandibular joint (TMJ) hypofunction secondary to feeding a liquid diet in the growing period leads to morphological hypoplasia. However, few studies have evaluated the results of mechanical loading on the hypoplastic TMJ. This study investigated whether TMJ hypofunction in rats causes osteoarthritis (OA)-like changes when exposed to mechanical loading.Archives of Oral Biology 08/2014; 59(12):1368-1376. DOI:10.1016/j.archoralbio.2014.08.010 · 1.88 Impact Factor
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ABSTRACT: Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found both early and late recombinant lubricin treatment attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to less effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X), matrix metalloproteinase (MMP-13) but increased the expression of Lubricin, in comparison with vehicle-treated OVX rats group. Further, Chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV), trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed lights on that both early and late recombinant lubricin treatment attenuate the onset of OA by balancing the interplay between artricular cartilage and subcondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting treatment timing is a pivotal factor for better effect acquisition. Copyright © 2015. Published by Elsevier Inc.Bone 01/2015; 74. DOI:10.1016/j.bone.2014.12.065 · 4.46 Impact Factor
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ABSTRACT: Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated.BMC Musculoskeletal Disorders 11/2014; 15(1):370. DOI:10.1186/1471-2474-15-370 · 1.90 Impact Factor