Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

Abstract

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions.

Molecular and Lifestyle Factors Modulating Obesity Disease

“…Mechanical loading signals can induce osteogenic and chondrogenic genes expression to the detriment of adipogenesis by activating the Wnt-β-catenin pathway [97]. Recently, we demonstrated that physical activity promotes the expression of important molecules such as the osteogenic determinant RUNX2 and of chondrogenic determinant SOX9 in circulating progenitors of male runners after a half marathon [98]. We also observed a reduced expression of the adipogenic determinant PPARG2 in these circulating progenitors after the half marathon [98].…”

“…Recently, we demonstrated that physical activity promotes the expression of important molecules such as the osteogenic determinant RUNX2 and of chondrogenic determinant SOX9 in circulating progenitors of male runners after a half marathon [98]. We also observed a reduced expression of the adipogenic determinant PPARG2 in these circulating progenitors after the half marathon [98]. However, many other genes have been suggested to influence adipogenic differentiation.…”

Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies

“…Indeed, environmental oxygen tension in articular chondrocytes has been shown to play an important role in determining their ability to counteract RONS exposure in OA [ 19 ]. In addition, we have demonstrated increased expression during physical activity of chondrogenic transcription factors SOX9 in circulating mesenchymal progenitors associated with autophagy [ 20 ]. This finding suggests the beneficial role of physical exercise in preserving chondrogenesis.…”

Exercise as an Adjuvant to Cartilage Regeneration Therapy

“…BMP2 and BMP6 were also upregulated. The authors concluded that exercise upregulated the differentiation and apoptosis of BM-MSCs [ 44 ]. In a study involving 20 amateur runners, Valenti et al assessed the effects of running one-half of a marathon on the expression of microRNAs (miRNAs) in human BM-MSCs incubated with pre- and post-exercise sera.…”