Extended Data Fig. 1: Effects of 6 weeks of running.

(a) Mean distance run per hour (n = 24 animals). (b) Mean daily distance over the course of 6 weeks (n = 16 animals). (c) changes in sedentary (n = 12) and exercising mice (n = 17, **p = 0.0076, two-tailed U test) compared to initial six weeks prior. (d) Heart weight adjusted for tibia length (n = 9 animals per group). (e) Food consumption during the last week of exercise (***p = 0.0002, n = 9 animals per group, two-tailed Student’s t-test). (f) Flow cytometry gating strategy for leukocytes in skeletal muscle. (g) Total leukocytes, neutrophils, monocytes and macrophages per mg muscle tissue by flow cytometry (n = 7 animals for sedentary, n = 12 for exercise). (h) Representative microCT images of the proximal metaphysis and mid-diaphysis tibia of exercising and sedentary mice. (i) Parameters of bone microstructure, including trabecular and cortical thickness, bone mineral density and polar moment of inertia by µCT (n = 6 animals per group). (j) Representative Runx2 staining of tibial proximal metaphysis. Osteoblast surface per bone surface (Ob.S/BS, n = 6 animals per group). (k) Bone formation rate as observed by incorporation of calcein (20 mg/kg, 7 days prior) and alizarin red (30 mg/kg, 2 days prior to sacrifice) during bone mineralization at the diaphysis of femurs. Distance of fluorescent label indicated by the arrow demarcates the mineralization front at different times of administration. ‘#’ denotes medullary cavity and ‘##’ trabecular bone (n = 4 animals). Data are mean ± s.e.m. We acknowledge Servier Medical Art (https://smart.servier.com) for providing images of mice and components of the cartoon.