Growth differentiation factor-15 as a modulator of bone and muscle metabolism

Abstract

This study aims to clarify the potential role of growth differentiation factor-15 (GDF-15) as a myokine in bone metabolism and muscle function in females with osteoporosis. In total, 45 female participants (71.0 ± 8.5 years) with distal radius fractures were recruited. Participants were classified as healthy/osteopenic (n = 28) (CON) or osteoporotic (n = 17) (OP) according to their T-score from the areal bone mineral density (aBMD) of the femoral neck. Body mass index, upper arm and calf circumferences, and handgrip strength were assessed. Total hip, femoral neck, and lumbar spine aBMD was measured via dual-energy x-ray absorptiometry. The focal bone quality of the distal radius was evaluated via 3D reconstructed computed tomographic images. Serum levels of GDF-15, insulin-like growth factor-1, and inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β (IL-1β), as well as the corresponding mRNA levels in the pronator quadratus muscle were determined. Participants in the OP group had higher serum GDF-15 levels than those in the CON group. The mRNA levels of GDF-15, IL-1β, and TNF-α in the pronator quadratus muscle were significantly higher in the OP group than in the CON one. Levels of both serum GDF-15 and GDF-15 mRNA in muscle were positively correlated with age and negatively associated with the aBMD of the total hip and focal bone quality of the distal radius. Handgrip power was not correlated with circulating GDF-15 levels but was correlated with circumferences of the upper arm and calf, and levels of GDF-15 mRNA in muscle specimens. The mRNA levels of GDF-15 were correlated with those of inflammatory cytokines such as TNF-α and IL-1β. The mRNA levels of TNF-α were associated with circumferences of the upper arm and calf and with the aBMD of the total hip. The mRNA levels of GDF-15 in muscle were correlated with serum levels of GDF-15 and TNF-α. GDF-15 may have associations with bone metabolism in humans via paracrinological and endocrinological mechanisms. Maintenance of muscle mass and function would be influenced more by GDF-15 in muscle than by circulating GDF-15. The role of GDF-15 in bone metabolism and muscle homeostasis could be related to inflammatory responses.

Sex-specific association of low-renin hypertension with metabolic and musculoskeletal health in Korean older adults

“…In contrast, another study in young men did not show any association between RBP4 and BMD (50). Furthermore, serum GDF15 level, which may affect bone metabolism or muscle homeostasis in old women via inflammatory responses (51), seemed to have positive linear correlation with the presence of LRH in the current study. Further research is essential to understand the role of RBP4 and GDF15 levels on musculoskeletal health in the older adults with LRH.…”

Targeting GDF15 as a potential therapy for low back pain originating from endplate

“…GDF15 has been proved to be a new biomarker for the diagnosis, progression or prognosis of the above diseases and become a new target for the development of drugs [17][18][19][20]46,47 . Previous study showed that, GDF15 is a myokine in bone metabolism and muscle function in females with osteoporosis 23,48 . However, the role of GDF15 on LBP has not been demonstrated.…”

Transcriptional Profiling of Muscle in Females With Distal Radius Fracture and Functional Sarcopenia

“…The pro-inflammatory cytokines including interleukin-6, TNF-α, and interleukin-1β on pathogenesis of sarcopenia and osteoporosis have been demonstrated previously ( 29–32 ). Among them, IL-6 and TNF-α appear to play a part in preserving muscle–bone homeostasis as myokines ( 18 , 33 ). Hence, the results from RNA sequencing data validated the importance of inflammatory response in molecular background muscle–bone interaction, as suggested in previous reports.…”