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]/cm³ [95% CI, 2.51 to 79.54 mg HA/cm³]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm³ [95% CI, 4.08 to 76.71 mg HA/cm³]; 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.

中文翻译：

---

乳酸通过诱导成骨细胞分化介导高强度间歇训练的骨合成代谢效应

背景： 

据报道，高强度间歇训练（HIIT）可以改善骨代谢并增加骨矿物质密度（BMD）。本研究的目的是在已建立的骨质疏松动物模型中研究乳酸是否介导运动对 BMD、骨微结构和生物力学特性的有益影响。此外，我们假设乳酸诱导的骨增量是通过增强成骨细胞分化和矿化来实现的。

方法： 

50只雌性C57BL/6小鼠随机分为5组:非卵巢切除组、卵巢切除组(OVX)、HIIT组(OVX+HIIT)、HIIT联合乳酸转运蛋白抑制组(OVX+HIIT+INH) ，以及乳酸皮下注射组（OVX + LAC）。干预7周后，通过显微计算机断层扫描（micro-CT）、生物力学测试、组织学分析和血清生化检测评估骨量、骨强度和骨形成/吸收过程；进行体外研究以探索乳酸在细胞水平上的骨合成代谢作用。

结果： 

Micro-CT 显示 OVX + HIIT 组的 BMD 显着增加（平均差，41.03 mg 羟基磷灰石 [HA]/cm ³ [95% CI，2.51 至 79.54 mg HA/cm ³ ]；p = 0.029）和 OVX + LAC 组（平均差，40.40 mg HA/cm ³ [95% CI，4.08 至 76.71 mg HA/cm ³]; p = 0.031）与 OVX 组相比。生物力学测试表明，这两组的机械性能显着改善。然而，运动对骨微结构和生物力学的有益影响在很大程度上因阻断乳酸转运蛋白而被消除。值得注意的是，组织学和生化结果表明，增加骨形成是 HIIT 和乳酸的增骨作用的原因。细胞培养研究表明，乳酸处理后成骨细胞标志物的表达显着增加，这可以通过阻断乳酸转运蛋白来消除。

结论： 

乳酸可能介导了骨质疏松小鼠中 HIIT 的骨合成代谢作用，这可能是由于成骨细胞分化和矿化增强所致。

临床相关性： 

乳酸可能介导 HIIT 的骨合成代谢作用，并可作为一种潜在的廉价骨增量治疗策略。