Disuse-induced bone loss is characterized by alterations in bone turnover. Accruing evidence suggests that osteocytes respond to inflammation and express and/or release pro-inflammatory cytokines; however, it remains largely unknown whether osteocyte inflammatory proteins are influenced by disuse. The goals of this project were (1) to assess osteocyte pro-inflammatory cytokines in the unloaded hindlimb and loaded forelimb of hindlimb unloaded rats, (2) to examine the impact of exogenous irisin during hindlimb unloading (HU). Male Sprague Dawley rats (8 weeks old, n = 6/group) were divided into ambulatory control, HU, and HU with irisin (HU + Ir, 3×/week). Lower cancellous bone volume, higher osteoclast surfaces (OcS), and lower bone formation rate (BFR) were present at the hindlimb and 4th lumbar vertebrae in the HU group while the proximal humerus of HU rats exhibited no differences in bone volume, but higher BFR and lower OcS vs. Con. Osteocyte tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), RANKL, and sclerostin were elevated in the cancellous bone of the distal femur of HU rats vs. Con, but lower at the proximal humerus in HU rats vs. Con. Exogenous irisin treatment increased BFR, and lowered OcS and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb of HU + Ir rats while having minimal changes in the humerus. In conclusion, there are site-specific and loading-specific alterations in osteocyte pro-inflammatory cytokines and bone turnover with the HU model of disuse bone loss, indicating a potential mechanosensory impact of osteocyte TNF-α and IL-17. Additionally, exogenous irisin significantly reduced the pro-inflammatory status of the unloaded hindlimb.

废用性骨质流失的特点是骨转换的改变。越来越多的证据表明，骨细胞对炎症有反应并表达和/或释放促炎细胞因子；然而，骨细胞炎症蛋白是否受到废弃的影响仍然很大程度上未知。该项目的目标是 (1) 评估后肢卸载大鼠的卸载后肢和加载前肢中的骨细胞促炎细胞因子，(2) 检查外源鸢尾素在后肢卸载 (HU) 期间的影响。雄性 Sprague Dawley 大鼠（8 周大，n = 6/组）分为非卧床对照、HU 和带有鸢尾素的 HU（HU + Ir，3×/周）。HU组的后肢和第4腰椎松质骨体积较低，破骨细胞表面（OcS）较高，骨形成率（BFR）较低，而HU大鼠肱骨近端骨体积无差异，但BFR较高和更低的 ocS vs. Con。与 Con 相比，HU 大鼠股骨远端松质骨中骨细胞肿瘤坏死因子-α (TNF-α)、白细胞介素-17 (IL-17)、RANKL 和硬化蛋白升高，但在 HU 肱骨近端降低老鼠与康。外源鸢尾素治疗增加了 HU + Ir 大鼠空载后肢的 BFR，并降低了 OcS 和骨细胞 TNF-α、IL-17、RANKL 和硬化蛋白，而肱骨的变化很小。综上所述，在废用性骨丢失的 HU 模型中，骨细胞促炎细胞因子和骨转换存在位点特异性和负荷特异性改变，表明骨细胞 TNF-α 和 IL-17 具有潜在的机械感觉影响。此外，外源性鸢尾素显着降低了空载后肢的促炎状态。