棕色脂肪组织分泌的Nrg4通过协调骨吸收和血管生成来防止骨丢失
Brown Adipose Tissue Secreted Nrg4 Prevents Bone Loss by Orchestrates Bone Resorption and Angiogenesis.
摘要(中文译文)
除在代谢调节中的既定作用外，脂肪组织来源因子日益被认为是骨量的关键调节因子。然而，协调破骨细胞生成-血管生成-成骨轴以维持骨骼稳态的潜在机制仍不明确。本研究采用棕色脂肪组织（BAT）去除、神经调节蛋白4（Nrg4）基因敲除（Nrg4）及BAT移植小鼠模型，评估BAT分泌的Nrg4在骨稳态中的作用。通过体外实验探讨Nrg4对破骨细胞生成及血管生成-成骨偶联的影响。此外，对卵巢切除（OVX）诱导的骨质疏松小鼠给予外源性Nrg4治疗，以评估其治疗潜力。BAT去除或Nrg4基因敲除导致骨吸收增加、骨形成减少，从而加速小鼠骨丢失；相反，BAT移植可挽救Nrg4小鼠的骨骼表型。体外实验中，Nrg4显著抑制破骨细胞生成，至少部分通过NF-κB炎症信号通路实现，同时通过前破骨细胞来源的PDGF-BB激活血管生成-成骨偶联。此外，外源性Nrg4治疗有效减轻OVX诱导的骨质疏松小鼠的骨丢失。这些发现表明，BAT来源的Nrg4是骨稳态的关键调节因子，通过协调破骨细胞与内皮细胞之间的交互对话，成为骨丢失疾病有前景的治疗靶点。
Abstract
Beyond established roles in metabolic regulation, adipose tissue-derived factors are increasingly recognized as critical modulators of bone mass. Nevertheless, the underlying mechanisms that coordinate the osteoclastogenesis-angiogenesis-osteogenesis axis to maintain skeletal homeostasis remain poorly defined. Mouse models including brown adipose tissue (BAT) removal, Neuregulin 4 (Nrg4) knockout (Nrg4), and BAT transplantation were used to evaluate the role of BAT-secreted Nrg4 in bone homeostasis. In vitro experiments were performed to explore the effects of Nrg4 on osteoclastogenesis and the angiogenesis-osteogenesis coupling. Additionally, exogenous Nrg4 treatment was applied to ovariectomy (OVX)-induced osteoporotic mice to assess its therapeutic potential. BAT removal or Nrg4 knockout resulted in increased bone resorption and decreased bone formation, thereby accelerating bone loss in mice; conversely, BAT transplantation rescued the skeletal phenotype of Nrg4 mice. In vitro, Nrg4 significantly inhibited osteoclastogenesis, at least partially through the NF-κB inflammatory signaling pathway, while simultaneously activating the angiogenesis-osteogenesis coupling via PDGF-BB derived from preosteoclasts. Furthermore, exogenous Nrg4 treatment effectively attenuated bone loss in OVX-induced osteoporotic mice. These findings demonstrate that BAT-derived Nrg4 acts as a key regulator of bone homeostasis and represents a promising therapeutic target for bone loss disorders by orchestrating crosstalk between osteoclasts and endothelial cells.
如何引用
AMA
Xiaoli Xu, Jianrong Zhou, Mengjia Tang, Yuping Zhang, Jiongyu Hu, Lingfeng Shi. Brown Adipose Tissue Secreted Nrg4 Prevents Bone Loss by Orchestrates Bone Resorption and Angiogenesis.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2026; doi:10.1096/fj.202601258RR.
APA
Xiaoli Xu, Jianrong Zhou, Mengjia Tang, Yuping Zhang, Jiongyu Hu, Lingfeng Shi (2026). Brown Adipose Tissue Secreted Nrg4 Prevents Bone Loss by Orchestrates Bone Resorption and Angiogenesis.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202601258RR
GB/T 7714
Xiaoli Xu, Jianrong Zhou, Mengjia Tang, Yuping Zhang, Jiongyu Hu, Lingfeng Shi. Brown Adipose Tissue Secreted Nrg4 Prevents Bone Loss by Orchestrates Bone Resorption and Angiogenesis.[J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026 doi:10.1096/fj.202601258RR.
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