Transduction. BRD2 and BRD4, both members of the BET-protein family, were recently shown to play a critical role in adipogenesis [19?1]. In the last years, we showed that N-methyl pyrrolidone (NMP), a small molecule used as a drug solvent and as a constituent in FDA-approved medical devices, targets osteoblast and osteoclast differentiation [22, 23]. Indeed, NMP has demonstrated to have polyvalent capabilities; it enhances BMP-2-induced osteoblast differentiation and bone regeneration and disturbs osteoclast differentiation and bone resorption [22, 23]. Recently, in an animal model of osteoporosis, we showed that NMP exhibits an anti-osteoporotic capability [24] while in an in vitro inflammation model, NMP attenuated the production of LPS induced pro-inflammatory cytokines [25]. Osteoblasts and adipocytes differentiate from a common precursor, bone marrow mesenchymal stem cells (BMSCs) [26, 27]. There is an estrogen-linked reduction in osteogenesis that is accompanied by an increase in adipogenesis. This switch increases white adipocytes and decreases osteoblasts numbers, triggering estrogen deficiency-related bone loss [28]. The goal of this study was to determine the effect of NMP on adipogenesis in vitro and white fat tissue accumulation and marrow fat content in an in vivo model of estrogen deficiencyinduced osteoporosis.ResultsPotency of NMP treatment on weight gain, bone marrow adiposity, and biomarkersOvariectomy significantly increased the body mass of animals, especially in the first 3 weeks after surgery (first 20 days of the study). OVX animals weighted 50 g more than their Sham counterparts and only 30 g more than the OVX NMP group, during these first 3 weeks (Fig. 1a). Over time, the body weight gain increased steadily but was less striking, although a difference of 70 g was visible between Sham Veh and OVX Veh groups by the end of the study, which equals a 20 weight increase. While throughout the duration of the treatment, NMP-treated animals gained significantly less weight than the OVX animals ( 40 g). It is known that weight gain after menopause is often due to the decline of estrogen levels. For this reason, we not only measured the body mass of the animals during this treatment but the levels of different biomarkers involved in weight regulation such as estrogen, TNF-, and leptin were also measured (Fig. 1c). Estradiol level in the OVX Veh group was significantly lower than in Sham Veh group. Even though there was an increase in estradiol level in OVX NMP group, no statistically significant difference was observed between OVX Veh and OVX NMP groups. The serum TNF- level was significantly more elevated in OVX Veh than in Sham Veh and NMP OVX animals. The same trend was observed for the serum leptin level (Fig. 1c). The three common HS-173 web findings in osteoporotic bone are increased levels of osteoclastogenesis, decreased osteoblastogenesis, and increased bone marrow adipogenesis. The first is associated with a lack of estrogens and therefore is more commonly PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28945807 seen in women during their postmenopausal years. The reduction in osteoblastogenesis, with the concomitant increase in adipogenesis, is the consequence of the shift in the differentiation of bone marrow cells predominantly into adipocytes [6]. The consequence of these changes is a progressively fatty bone with reduced bone mass. As shown in the Fig. 1b, estrogen deficiency increases fat accumulation in the bone marrow. The NMP treatment of ovariectomized animal coun.