Lactate Mediates the Bone Anabolic Effect of High-Intensity Interval Training by Inducing Osteoblast Differentiation

骨矿物 间歇训练 骨重建 内分泌学 内科学 去卵巢大鼠 合成代谢 骨吸收 成骨细胞 骨质疏松症 化学 乳酸脱氢酶 高强度间歇训练 医学 激素 体外 生物化学
作者
Zhenglin Zhu,Yi Chen,Jing Zou,Shengqiang Gao,Dandong Wu,Xuelun Li,Ning Hu,Jinzhong Zhao,Wei Huang,Hong Chen
出处
期刊:Journal of Bone and Joint Surgery, American Volume [Journal of Bone and Joint Surgery]
卷期号:105 (5): 369-379 被引量:6
标识
DOI:10.2106/jbjs.22.01028
摘要

Background: High-intensity interval training (HIIT) reportedly improves bone metabolism and increases bone mineral density (BMD). The purpose of the present study was to investigate whether lactate mediates the beneficial effects of exercise on BMD, bone microarchitecture, and biomechanical properties in an established osteoporotic animal model. In addition, we hypothesized that lactate-induced bone augmentation is achieved through enhanced osteoblast differentiation and mineralization. Methods: A total of 50 female C57BL/6 mice were randomly allocated into 5 groups: the nonovariectomized group, the ovariectomized group (OVX), the HIIT group (OVX + HIIT), the HIIT with lactate transporter inhibition group (OVX + HIIT + INH), and the lactate subcutaneous injection group (OVX + LAC). After 7 weeks of intervention, bone mass, bone strength, and bone formation/resorption processes were evaluated via microcomputed tomography (micro-CT), biomechanical testing, histological analysis, and serum biochemical assays; in vitro studies were performed to explore the bone anabolic effect of lactate at the cellular level. Results: Micro-CT revealed significantly increased BMD in both the OVX + HIIT group (mean difference, 41.03 mg hydroxyapatite [HA]/cm 3 [95% CI, 2.51 to 79.54 mg HA/cm 3 ]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm 3 [95% CI, 4.08 to 76.71 mg HA/cm 3 ]; p = 0.031) compared with the OVX group. Biomechanical testing demonstrated significantly improved mechanical properties in those 2 groups. However, the beneficial effects of exercise on bone microstructure and biomechanics were largely abolished by blocking the lactate transporter. Notably, histological and biochemical results indicated that increased bone formation was responsible for the bone augmentation effects of HIIT and lactate. Cell culture studies showed a marked increase in the expression of osteoblastic markers with lactate treatment, which could be eliminated by blocking the lactate transporter. Conclusions: Lactate may have mediated the bone anabolic effect of HIIT in osteoporotic mice, which may have resulted from enhanced osteoblast differentiation and mineralization. Clinical Relevance: Lactate may mediate the bone anabolic effect of HIIT and serve as a potential inexpensive therapeutic strategy for bone augmentation.
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