| dc.description.abstract | A growing body of evidence has shown that exercise can stimulate the release of proteins from skeletal muscle, termed myokines, that work in a hormone-like fashion and exert specific endocrine effects on distant organs. In our study, we have found that FNDC5 (irisin) and fibroblast growth factor 21 (FGF21) were up-regulated by MyoD. N-lactoyl-phenylalanine (N-LP) is a newly identified metabolite synthesized from lactate and phenylalanine by the enzyme carnosine dipeptidase 2（CNDP2）in various cells after strenuous exercise, and it share similar effect with irisin/FGF21 on adipocytes, such as oxidative metabolism enhancement. In this study, we aim to investigate the relationship between irisin/FGF21 and N-LP in skeletal muscle and their synergistic effect on the musculoskeletal system. We found that the promoter activity of FGF21 was activated by MyoD, N-LP, and the neurotransmitter acetylcholine (Ach) but repressed by cytokines TNFα and IL-1β, suggesting its activation by differentiation and exercise signals. Additionally, although either Ach or N-LP can enhance FGF21 promoter activity in GM or DM, together they repressed FGF21 promoter in DM, implying antagonistic pathways are involved in their signaling. MC3T3 osteoblast cells were treated with N-LP and irisin/FGF21 to analyze their distinct and synergistic effect on osteogenesis. We found that N-LP enhanced osteogenesis starting from early stage but the effect of irisin/FGF21 could only be seen at late stage, especially the activation of the osteogenic gene Osteopontin. Our results provide new relationship between myokines and the exercise metabolite N-LP, and N-LP might become a new therapy for osteoporosis or related diseases. | en_US |