Metformin attenuates high-fat diet induced metabolic syndrome related osteoarthritis through inhibition of prostaglandins.

Metformin attenuates high-fat diet induced metabolic syndrome related osteoarthritis through inhibition of prostaglandins.
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DOI:
10.3389/fcell.2023.1184524
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发表时间:
2023
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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高脂饮食会诱发膝关节骨髓炎症和骨关节炎表型,但其潜在机制尚不清楚。在这里,我们报告高脂肪饮食会导致膝关节骨形成异常和软骨退化。从机制上讲,高脂肪饮食会增加软骨下骨中巨噬细胞的数量和前列腺素的分泌,从而促进骨形成。二甲双胍治疗能够减少软骨下骨中巨噬细胞的数量以及高脂肪饮食诱导的前列腺素水平。重要的是,二甲双胍通过减少骨祖细胞和 H 型血管的数量来挽救异常的骨形成和软骨损伤,这也可以缓解骨关节炎的疼痛反应。因此,我们证明巨噬细胞分泌的前列腺素可能是高脂饮食诱导异常骨形成的关键原因,二甲双胍是治疗高脂饮食诱导的骨关节炎的有前途的疗法。
High-fat diet induces bone marrow inflammation and osteoarthritis phenotype in knee joint, but the underlying mechanisms is unknown. Here, we report that high-fat diet induces aberrant bone formation and cartilage degeneration in knee joint. Mechanistically, a high-fat diet increases the number of macrophages and the secretion of prostaglandins in subchondral bone, promoting bone formation. Metformin treatment is able to decrease the number of macrophages and also the level of prostaglandins induced by high-fat diet in subchondral bone. Importantly, metformin rescues aberrant bone formation and cartilage lesions by decreasing the number of osteoprogenitors and type-H vessels, which also results in relief of osteoarthritis pain response. Thus, we demonstrate prostaglandins secreted by macrophages may be a key reason for high-fat diet induced aberrant bone formation and metformin is a promising therapy for high-fat diet induced osteoarthritis.
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