Novel DNA aptamer activating skeletal muscle stem cells

Novel DNA aptamer activating skeletal muscle stem cells

Tomohide Takaya.

Institute for Biomedical Sciences, Shinshu University, Nagano, Japan.

Symposium on Advanced Materials and 3D Printing for Biomedical Applications, The 7th Institute for Biomedical Sciences International Symposium (Matsumoto, Japan), 2017/10/20 (Talk).

Abstract

Skeletal muscle, which generates a great power for active behaviors, is the largest tissue in human. However, muscle strength and mass gradually decrease with aging. To improve quality of life, muscle atrophy should be prevented in aging societies. Skeletal muscle regeneration is maintained by somatic stem cells existing on myofibers, called satellite cells. Physical and hormonal signals activate satellite cells into myoblasts as myogenic progenitor cells. Myoblasts proliferate then differentiate into contractile myocytes to regenerate skeletal muscle.

To prevent muscle atrophy, we have been trying to find the molecules acting on myoblasts. Recently, we successfully identified a series of DNA aptamers (short and single-strand nucleotides) which intensively induce myogenic differentiation of myoblasts into mature myocytes. These aptamers named "myoDN" (myogenic oligodeoxynucleotide) were generated from the genomic sequence of lactic acid bacterium, Lactobacillus rhamnosus GG. Interestingly, our results indicated that the 3D structure of myoDN is critically important for its activity. Computational simulation and mutational analyses demonstrated the telomeric repeat is a core domain of myoDN.

We hypothesized that stabilization of myoDN structure may enhance its myogenic activity. Berberine, an alkaloid from Phellodendron amurense, has been known to bind to telomeric sequence. Predictably, berberine interacted with myoDN to form complex. Berberine alone had no effects on myoblasts but myoDN- berberine complex showed higher activity compared with myoDN alone.

Promoting myogenic differentiation by myoDN with berberine will be useful for prevention and treatment of age-related skeletal muscle atrophy. myoDN will hopefully be a novel functional material used as drugs or food supplements.