Bone–muscle crosstalk following exercise plus Ursolic acid by myomiR-133a/Cx43-Runx2 axis in aged type 2 diabetes rat models

Natural bioactive compound, Ursolic acid (UA), plus different types of exercise may exert the action on glycemic control, leading to clinical benefits in the prevention and treatment of aging/diabetes-associated complications. So, this study examined the effects of eight weeks combination of 250 mg of UA per day per kilogram of body weight of rat as well as resistance/endurance training on miR-133a expression across serum, bone marrow, skeletal muscle, and Connexin 43 (Cx43)-Runt-related transcription factor 2 (Runx2) signaling axis in high-fat diet and low-dose streptozotocin-induced T2D (here, HFD/STZ-induced T2D). The study was conducted on 56 male Wistar rats (427 ± 44 g, 21 months old), having HFD/STZ-induced T2D randomly assigned into 7 groups of 8 including (1) sedentary non-diabetic old rats (C); (2) sedentary type 2 diabetes animal model (D); (3) sedentary type 2 diabetes animal model + UA (DU); (4) endurance-trained type 2 diabetes animal model (DE); (5) resistance-trained type 2 diabetes animal model (DR); (6) endurance-trained type 2 diabetes animal model + UA (DEU); and (7) resistance-trained type 2 diabetes animal model + UA (DRU). Resistance training included a model of eight weeks of ladder resistance training at 60–80% maximal voluntary carrying capacity (MVCC) for five days/week. Treadmill endurance exercise protocol included eight weeks of repetitive bouts of low-/high-intensity training with 30%–40% and 60%–75% maximal running speed for five days/week, respectively. UA Supplementary groups were treated with 500 mg of UA per kg of high-fat diet per day. The results revealed significant supplement and exercise interaction effects for the BM miR-133a (p = 0.001), the bone marrow Runx2 (p = 0.002), but not the serum miR-133a (p = 0.517), the skeletal muscle miR-133a (p = 0.097) and the Cx43 (p = 0.632). In conclusion, only eight weeks of resistance-type exercise could affect miR-133a profile in muscles and osteoblast differentiation biomarker RUNX2 in aged T2D model of rats. 250 mg of UA per kilogram of body weight rat per day was administered orally, less than the sufficient dose for biological and physiological impacts on osteoblast differentiation biomarkers in aged T2D model of rats following eight weeks.