Muscle-Bone Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches to Treat Musculoskeletal Pathologies

Abstract

Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that often develop in parallel. Osteoporosis is characterized by a reduced bone mass and an increased fracture risk. Sarcopenia describes muscle wasting with an increasing risk of injuries due to falls. The medical treatment of both diseases costs billions in health care per year. With the impact on public health and economy, and considering the increasing life expectancy of populations, more efficient treatment regimens are sought. The biomechanical interaction between both tissues with muscle acting on bone is well established. Recently, both tissues were also determined as secretory endocrine organs affecting the function of one another. New exciting discoveries on this front are made each year, with novel signaling molecules being discovered and potential controversies being described. While this review does not claim completeness, it will summarize the current knowledge on both the biomechanical and the biochemical link between muscle and bone. The review will highlight the known secreted molecules by both tissues affecting the other and finish with an outlook on novel therapeutics that could emerge from these discoveries.

Keywords: biomechanical; bone; crosstalk; hormones; muscle; therapeutics.

Figure 1

Using the search term “musculoskeletal interaction”, this graph demonstrated the increase in published papers in recent years with regard to the topic. The search has been made using PubMed, in September 2017.

Figure 2

Role of vessels in the muscle–bone crosstalk: (A) Presence of vessels coming from the skeletal muscle in bone (white arrowheads). The vessels are stained in green, in transgenic mice model Flk1-GFP, where the green fluorescent protein is driven by a promoter targeting a receptor of VEGF-A [50]. Magnification: 10×; (B) physical connection between osteocytes in the femur (stained in red by a Dextran-lysine fixable stain) and a vessel, in green (Flk1-GFP mice) (white arrowhead). Magnification: 63×. Scale bars represent: 100 μm (A); and 25 μm (B).