The role of PPAR gamma in childhood obesity-induced fractures

Abstract

Globally, obesity is on the rise with similar to 30% of the world's population now obese, and childhood obesity is following similar trends. Childhood obesity has been associated with numerous chronic conditions, including musculoskeletal disorders. This review highlights the effects of childhood adiposity on bone density by way of analyzing clinical studies and further describing two severe skeletal conditions, slipped capital femoral epiphysis and Blount's disease. The latter half of this review discusses bone remodeling and cell types that mediate bone growth and strength, including key growth factors and transcription factors that help orchestrate this complex pathology. In particular, the transcriptional factor peroxisome proliferator-activated receptor gamma (PPAR gamma) is examined as it is a master regulator of adipocyte differentiation in mesenchymal stem cells (MSCs) that can also influence osteoblast populations. Obese individuals are known to have higher levels of PPAR gamma expression which contributes to their increased adipocyte numbers and decreased bone density. Modulating PPAR*gamma* signaling can have significant effects on adipogenesis, thereby directing MSCs down the osteoblastogenesis pathway and in turn increasing bone mineral density. Lastly, we explore the potential of PPAR gamma as a druggable target to decrease adiposity, increase bone density, and be a treatment for children with obesity-induced bone fractures.