Globally, obesity is on the rise with ~ 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 (PPARγ) 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 PPARγ 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 PPARγ as a druggable target to decrease adiposity, increase bone density, and be a treatment for children with obesity-induced bone fractures.

中文翻译：

---

PPARγ在儿童肥胖性骨折中的作用

在全球范围内，肥胖症正在增加，目前全世界约30％的人肥胖，而儿童肥胖症也遵循类似的趋势。儿童肥胖与许多慢性疾病有关，包括肌肉骨骼疾病。这篇综述通过分析临床研究并进一步描述了两种严重的骨骼疾病，即股骨骨epi滑脱和布朗特氏病，突出了儿童肥胖对骨密度的影响。本文的后半部分讨论了介导骨骼生长和强度的骨骼重塑和细胞类型，包括有助于协调这种复杂病理的关键生长因子和转录因子。尤其是，我们检查了转录因子过氧化物酶体增殖物激活受体γ（PPARγ），因为它是间充质干细胞（MSC）中脂肪细胞分化的主要调节剂，它也可能影响成骨细胞的数量。已知肥胖的个体具有较高水平的PPARγ表达，这有助于其增加的脂肪细胞数量和降低的骨密度。调节PPAR *γ*信号传导可对脂肪生成产生重大影响，从而将MSC引导至成骨细胞生成途径，进而增加骨矿物质密度。最后，我们探讨了PPARγ作为降低肥胖，增加骨密度和作为肥胖引起的儿童骨折的药物治疗目标的潜力。已知肥胖的个体具有较高水平的PPARγ表达，这有助于其增加的脂肪细胞数量和降低的骨密度。调节PPAR *γ*信号传导可对脂肪生成产生重大影响，从而将MSC引导至成骨细胞生成途径，进而增加骨矿物质密度。最后，我们探讨了PPARγ作为降低肥胖，增加骨密度和作为肥胖引起的儿童骨折的药物治疗目标的潜力。已知肥胖的个体具有较高水平的PPARγ表达，这有助于其增加的脂肪细胞数量和降低的骨密度。调节PPAR *γ*信号传导可对脂肪形成产生重大影响，从而将MSC引导至成骨细胞生成途径，进而增加骨矿物质密度。最后，我们探讨了PPARγ作为降低肥胖，增加骨密度和作为肥胖引起的儿童骨折的药物治疗目标的潜力。