PGC-1: a key regulator in bone homeostasis

Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) is an inducible co-regulator of nuclear receptors and is involved in a wide variety of biological responses. As the master regulators of mitochondrial biogenesis and function, PGC-1α and PGC-1β have been reported to play key roles in bone metabolism. They can be rapidly induced under conditions of increased metabolic activities, such as osteoblastogenesis and osteoclastogenesis, to fulfill greater energy demand or facilitate other biochemical reactions. PGC-1α and PGC-1β have both overlapping and distinct functions with each other among their target organs. In bone homeostasis, PGC-1α and PGC-1β promote the expression of genes required for mitochondrial biogenesis via coactivator interactions with key transcription factors, respectively regulating osteoblastogenesis and osteoclastogenesis. Here, we review the current understanding of how PGC-1α and PGC-1β affect osteoblastogenesis and osteoclastogenesis, how these two PGC-1 coactivators are regulated in bone homeostasis, and how we can translate these findings into therapeutic potential for bone metabolic diseases.