The Role of the Molecular Clock in Skeletal Muscle and What It Is Teaching Us About Muscle-Bone Crosstalk

Lance A. Riley, Karyn A. Esser

This review summarizes what has been learned about the interaction between skeletal muscle and bone from mouse models in which BMAL1, a core molecular clock protein has been deleted. Additionally, we highlight several genes which change following loss of BMAL1. The protein products from these genes are secreted from muscle and have a known effect on bone homeostasis. Circadian rhythms have been implicated in regulating systems homeostasis through a series of transcriptional-translational feedback loops termed the molecular clock. Recently, skeletal muscle-specific disruption of the molecular clock has been shown to disrupt skeletal muscle metabolism. Additionally, loss of circadian rhythms only in adult muscle has an effect on other tissue systems including bone. Our finding that the expression of a subset of skeletal muscle-secreted proteins changes following BMAL1 knockout combined with the current knowledge of muscle-bone crosstalk suggests that skeletal muscle circadian rhythms are important for maintenance of musculoskeletal homeostasis. Future research on this topic may be important for understanding the role of the skeletal muscle molecular clock in a number of diseases such as sarcopenia and osteoporosis.