The biological and molecular interactions of sarcopenia and bone loss in chronic kidney disease

Patients with chronic kidney disease (CKD) suffer profound musculoskeletal functional decline that is compounded by concurrent losses in bone mass (osteoporosis and renal bone disease) and skeletal muscle mass (sarcopenia) in conjunction with accumulation of adipose tissue. These effects result in reduced mobility and high rates of falls and fractures, incurring personal suffering and loss of quality of life. There is no effective pharmacological treatment for sarcopenia – making this a major unmet clinical need. We know that the interaction between bone and skeletal muscle is beyond simple mechanical coupling, with evidence that these tissues communicate at a biomolecular level. The growing knowledge base of the crosstalk between bone and muscle largely stems from monolayer cell culture models where the effects of individual osteokines on myoblasts or myotubes were studied and vice versa, which do not faithfully recapitulate the complex in vivo environments. Furthermore, the impact of a uraemic milieu on the bone-muscle biochemical interaction is not well studied. To overcome limitations in the current approach of studying these tissues in isolation, we are developing co-culture systems which will enable the investigation of the intricate biochemical interactions between these tissues. This will allow us to investigate the secretory and transcription factors which might be involved in the regulation of cell growth, induction of cell differentiation and production of metabolites for signalling cascades; information that is vital to understanding this widespread process more fully and the subsequent development of effective therapies.