Cho Dae-Chul, Brennan Holly J, Johnson Rachelle W, Poulton Ingrid J, Gooi Jonathan H, Tonkin Brett A, McGregor Narelle E, Walker Emma C, Handelsman David J, Martin T J, Sims Natalie A
St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, VIC, 3065, Australia.
Department of Neurosurgery, Kyungpook National University Hospital, 130 Dongdukro, Jung-gu, Daegu, 41944, Republic of Korea.
Nat Commun. 2017 Oct 9;8(1):806. doi: 10.1038/s41467-017-00920-x.
Long bone strength is determined by its outer shell (cortical bone), which forms by coalescence of thin trabeculae at the metaphysis (corticalization), but the factors that control this process are unknown. Here we show that SOCS3-dependent cytokine expression regulates bone corticalization. Young male and female Dmp1Cre.Socs3 mice, in which SOCS3 has been ablated in osteocytes, have high trabecular bone volume and poorly defined metaphyseal cortices. After puberty, male mice recover, but female corticalization is still impaired, leading to a lasting defect in bone strength. The phenotype depends on sex-steroid hormones: dihydrotestosterone treatment of gonadectomized female Dmp1Cre.Socs3 mice restores normal cortical morphology, whereas in males, estradiol treatment, or IL-6 deletion, recapitulates the female phenotype. This suggests that androgen action promotes metaphyseal corticalization, at least in part, via IL-6 signaling.The strength of long bones is determined by coalescence of trabeculae during corticalization. Here the authors show that this process is regulated by SOCS3 via a mechanism dependent on IL-6 and expression of sex hormones.
长骨强度由其外壳（皮质骨）决定，皮质骨通过干骺端细小梁的融合形成（皮质化），但控制这一过程的因素尚不清楚。在这里，我们表明依赖于细胞因子信号转导抑制因子3（SOCS3）的细胞因子表达调节骨皮质化。在骨细胞中SOCS3已被敲除的年轻雄性和雌性Dmp1Cre.Socs3小鼠，具有高骨小梁体积和界限不清的干骺端皮质。青春期后，雄性小鼠恢复正常，但雌性小鼠的皮质化仍受损，导致骨强度持续缺陷。该表型取决于性类固醇激素：对去势雌性Dmp1Cre.Socs3小鼠进行二氢睾酮治疗可恢复正常皮质形态，而在雄性小鼠中，雌二醇治疗或白细胞介素-6（IL-6）缺失可重现雌性表型。这表明雄激素作用至少部分通过IL-6信号通路促进干骺端皮质化。长骨强度由皮质化过程中小梁的融合决定。在这里，作者表明这一过程由SOCS3通过依赖于IL-6和性激素表达的机制进行调节。
