The Role of TGFβ in Bone-Muscle Crosstalk.
The role of bone-derived factors in regulation of skeletal muscle function is an important emerging aspect of research into bone-muscle crosstalk. Implications for this area of research are far reaching and include understanding skeletal muscle weakness in cancer, osteoporosis, cachexia, rare diseases of bone, and aging.



Recent research shows that bone-derived factors can lead to changes in the skeletal muscle. These changes can either be anabolic or catabolic, and we focus this review on the role of TGFβ in driving oxidative stress and skeletal muscle weakness in the setting of osteolytic cancer in the bone. The bone is a preferred site for breast cancer metastasis and leads to pathological bone loss. Osteolytic cancer in the bone leads to release of TGFβ from the bone via osteoclast-mediated bone destruction. Our appreciation of crosstalk between the muscle and bone has recently expanded beyond mechanical force-driven events to encompass a variety of signaling factors originating in one tissue and communicating to the other. This review summarizes some previously known mediators of bone-to-muscle signaling and also recent work identifying a new role for bone-derived TGFβ as a cause of skeletal muscle weakness in the setting of osteolytic cancer in the bone. Multiple points of potential therapeutic intervention are discussed.
Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Jenna N
JN
Regan
Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Trupti
T
Trivedi
Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Theresa A
TA
Guise
The Pennsylvania State University College of Medicine, 500 University Drive, H166, Rm C4710E, Hershey, PA, 17033, USA. dwaning@psu.edu.
David L
DL
Waning
D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D018908:Muscle Weakness / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta
Bone; Bone-muscle crosstalk; Skeletal muscle; TGFβ