The adiponectin agonist AdipoRon accelerates osteoporosis development in two different models and modulates adipocyte differentiation

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-09-03 DOI:10.1016/j.bone.2025.117628

Julia Halper , Sarah Nicolas , Federica Gilardi , Carine Winkler , Maria Materozzi , Mariano Schiffrin , Jean-Yves Jouzeau , Claudine Blin-Wakkach , Beatrice Desvergne , Joelle Chabry , Didier F. Pisani , David Moulin

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引用次数: 0

Abstract

Osteoporosis is an increasing concern in the aging population worldwide, culminating in increased economic concerns and diminished quality of life. Similarly, disturbances of lipid metabolism and adipocytes accumulate more and more in western societies and need solutions. Adipocytes have recently attracted much interest in relation to their endocrine products, one of which is adiponectin, normally associated with beneficial effects on cardiovascular health, inflammation, and cancer. In this study, we have investigated the effect of AdipoRon, an adiponectin receptor agonist with reported anti-osteoclastic properties, on the development of osteoporosis in two different preclinical models. Contrasting to our initial hypothesis, AdipoRon treatment accelerated metabolic changes and bone loss in both models. However, AdipoRon rescued bone marrow adipocytes presence induced by glucocorticoids. Investigations on adipocyte differentiation revealed that AdipoRon potently changes adipocyte identity, by exerting opposite effects on adipocyte-gene induction depending on the time point and duration of stimulation. In conclusion, adipocyte-derived Adiponectin deserves further investigation as an autocrine mediator in musculoskeletal research.

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脂联素激动剂AdipoRon在两种不同的模型中加速骨质疏松症的发展并调节脂肪细胞分化。

骨质疏松症是全球老龄化人口日益关注的问题，最终导致经济问题的增加和生活质量的下降。同样，在西方社会，脂质代谢和脂肪细胞的紊乱也越来越多，需要解决。脂肪细胞最近引起了人们对其内分泌产物的兴趣，其中之一是脂联素，通常与心血管健康、炎症和癌症的有益作用有关。在这项研究中，我们在两种不同的临床前模型中研究了AdipoRon（一种具有抗破骨特性的脂联素受体激动剂）对骨质疏松症发展的影响。与我们最初的假设相反，在两种模型中，AdipoRon治疗加速了代谢变化和骨质流失。然而，AdipoRon挽救了糖皮质激素诱导的骨髓脂肪细胞的存在。对脂肪细胞分化的研究表明，根据刺激的时间点和持续时间，AdipoRon对脂肪细胞基因诱导产生相反的作用，从而可能改变脂肪细胞的特性。总之，脂肪细胞来源的脂联素作为自分泌介质在肌肉骨骼研究中值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.