Work

Humanin improves bone health in a glucocorticoid-treated mouse model of Duchenne muscular dystrophy

Year: 2026

Type: article

Abstract: Duchenne muscular dystrophy (DMD) is a progressive muscle disease for which glucocorticoid (GC) treatment is standard therapy. Patients typically suffer from short stature and osteoporosis, caused by the underlying disease and adverse effects of GCs. We investigated whether the mitochondrial peptide humanin (HNG) could prevent GC-induced growth retardation and osteoporosis in mouse models of DMD. Male mdx mice (B10.mdx and D2.mdx) were treated with GCs, with/without HNG, from 5 to 9 weeks of age using two different treatment regimens. Tibial growth was monitored by weekly X-ray imaging; growth plates analyzed with immunohistochemistry and histomorphometry; and bone structure examined using peripheral quantitative computed tomography. Effects on skeletal muscle were evaluated by immunohistochemistry, qPCR, and ex vivo force measurements. D2.mdx, but not B10.mdx, showed decreased bone growth and impaired bone structure compared with wild type (WT). D2.mdx also displayed increased growth plate height with lower endogenous humanin expression than D2.WT. GC treatment caused growth retardation and reductions in cortical bone area, thickness, and mineral content. Co-administration with HNG prevented bone growth impairment at one week of treatment and mitigated GC adverse effects on cortical bone in B10.mdx mice. Adding HNG to GCs did not exacerbate skeletal muscle pathology; in fact, HNG had a mild enlarging effect on muscle fibers. These data suggest that HNG is a potential candidate for improving bone health in DMD during GC therapy. Further in vivo studies are needed to determine optimal HNG dosing and to assess the effects of long-term treatment on skeletal muscle function. • D2.mdx, not B10.mdx, showed compromised bone growth and structure vs. wild type. • Adding HNG to GC treatment mitigated GC-induced growth suppression the first week. • HNG mitigated GC's negative effects on cortical bone. • Adding HNG to GC treatment did not exacerbate muscle pathology.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2025.102421