Treadmill training prevents bone loss by inhibition of PPARγ expression but not promoting of Runx2 expression in ovariectomized rats

Abstract

Exercise training has been reported to prevent bone loss in ovariectomized (OVX) rats and postmenopausal women. We hypothesized that treadmill training inhibited adipogenesis and enhanced osteogenesis through the regulation of adipocyte differentiation factor peroxisome proliferators-activated receptor gamma (PPARγ) and the osteogenic factor runt-related transcription factor 2 (Runx2) in a model of OVX-induced osteoporosis. To test this hypothesis, 3-month-old female Sprague-Dawley rats were divided randomly into the following groups: Sham, OVX, OVX exercised (EX), and OVX estrogen replacement (E(2)). At the end of the experiment, the bone mineral density (BMD) was detected using DEXA and the morphology change of bone tissues and uterus was observed by HE staining. The protein expression for PPARγ and Runx2 were measured by immunohistochemistry and western blot and the bone triacylglycerol (TG) was extracted by methanol/chloroform. OVX dramatically increased the number of fat vacuoles, protein levels for PPARγ and Runx2 as well as the TG level in tibiae and lumbar vertebrate. In contrast, the serum level of E(2), the lumbar vertebrate BMD as well as the proximal and distal femur BMD was significantly decreased in the OVX group. All changes induced by OVX were significantly reversed by exercise treatment except for the protein expression level of Runx2. Moreover, exercise treatment produced no estrogenic effects on uterus as evidenced by the uterus wet weight and histology. Treadmill training could prevent bone loss induced by OVX through the inhibition of adipocyte differentiation factor PPARγ rather than promoting osteogenic factor Runx2.

MR spectroscopy and micro-CT in evaluation of osteoporosis model in rabbits: comparison with histopathology

“…Increased production of fat-related factors, such as fatty acids, could alter the fat-bone marrow relationship and inhibit hematopoiesis and/or osteogenesis [10]. Accumulating evidence from in vitro and in vivo studies suggests that the mesenchymal stem cell (MSCs) is the marrow precursor for adipocytes as well as osteoblasts [24][25][26][27]. The interaction between bone and fat formation is influenced by a multitude of factors including genetic, metabolic, and physical inputs to coordinate an appropriate adaptive response.…”

“…Activation of PPARγ positively regulates adipocyte differentiation while acting as a dominant negative regulator of osteogenic differentiation, inducing cells to shift to differentiated adipocytes. On the other hand Runx2 positively regulates osteogenic differentiation [25]. It is now known that oestrogen acts directly on both osteoblasts [28], osteoclasts [29].…”

trans-10,cis-12 Conjugated linoleic acid promotes bone formation by inhibiting adipogenesis by peroxisome proliferator activated receptor-γ-dependent mechanisms and by directly enhancing osteoblastogenesis from bone marrow mesenchymal stem cells

“…As immobilization is known to be linked to increased bone loss, physical activity (or exercise) has been shown positive effect on bone health. Morever, Chen et al (2011) recently reported the involvement of PPARγ on bone mass using treadmill exercise in ovariectomized rats. These results demonstrated that CLA might improve bone health by modulating physical activity.…”

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

“…138 This was also observed in ovariectomized rats given access to treadmill running: a reduction in MAT and prevention of bone loss. 139 While this inverse bone-to-fat relationship has been observed in several models, it is not always the case, as evidenced in certain mouse strains, such as C3H mice, which experience an increase in both bone and MAT. 78,140 However, while there was a suppression of PPAR-␥ , master regulator of adipogenesis, they did not observe an increase in RUNX2, master regulator of osteoblastogenesis, indicating that this relationship might not always be one-to-one.…”