Physical activity is widely recognized as a biotherapy by WHO in the fight and prevention of bone diseases such as osteoporosis. It reduces the risk of disabling fractures associated with many comorbidities, and whose repair is a major public health and economic issue. Bone tissue is a dynamic supportive tissue that reshapes itself according to the mechanical stresses to which it is exposed. Physical exercise is recognized as a key factor for bone health. However, the effects of exercise on bone quality depend on exercise protocols, duration, intensity, and frequency. Today, the effects of different exercise modalities on capillary bone vascularization, bone blood flow, and bone angiogenesis remain poorly understood and unclear. As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis–osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials. Thus, this review aimed to clarify the link between physical activities, vascularization, and bone repair.

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone defects in rats by µCT. We hypothesized that a preemptive running exercise would quicken bone healing. Twenty 5-week-old, male, Wistar rats were randomly allocated to one of the following groups (n = 10): sedentary control (SED) or continuous running (EX, 45 min/d, 5 d/week at moderate speed, for 8 consecutive weeks). A 2 mm diameter bone defect was then performed in the right tibia and femur. No exercise was performed during a 4 week-convalescence. Healing-tissue trabecular microarchitectural parameters were assessed once a week for 4 weeks using µCT and plasma bone turnover markers measured at the end of the study protocol (time point T12). At T12, bone volume fraction (BV/TV; BV: bone volume, TV: tissue volume) of the healing tissue in tibiae and femurs from EX rats was higher compared to that in SED rats (p = 0.001). BV/TV in EX rats was also higher in tibiae than in femurs (p < 0.01). The bone mineral density of the healing tissue in femurs from EX rats was higher compared to that in femurs from SED rats (p < 0.03). N-terminal telopeptide of collagen type I in EX rats was decreased compared to SED rats (p < 0.05), while no differences were observed for alkaline phosphatase and parathyroid hormone. The study provides evidence that preemptive moderate continuous running improves the healing of non-critical sized bone defects in male Wistar rats.

Physical exercise (PE) has unquestionable beneficial effects on health, which likely extend into several organ-to-cell physiological processes. At the cell scale, endogenous mesenchymal stromal cells (MSCs) contribute to tissue repair, although their repair capacities may be insufficient in paucicellular or severely damaged tissues. For this reason, MSC transplantation holds great promise for tissue repair. With the goals of understanding if PE has beneficial effects on MSC biology and if PE potentiates their role in tissue repair, we reviewed literature reports regarding the effects of PE on MSC properties (specifically, proliferation, differentiation, and homing) and of a combination of PE and MSC transplantation on tissue repair (specifically neural, cartilage, and muscular tissues). Contradictory results have been reported; interpretation is complicated because various and different species, cell sources, and experimental protocols, specifically exercise programs, have been used. On the basis of these data, the effects of exercise on MSC proliferation and differentiation depend on exercise characteristics (type, intensity, duration, etc.) and on the characteristics of the tissue from which the MSCs were collected. For the in vitro studies, the level of strain (and other details of the mechanical stimulus), the time elapsed between the end of exposure to strain and MSC collection, the age of the donors, as well as the passage number at which the MSCs are evaluated also play a role. The combination of PE and MSC engraftment improves neural, cartilage, and muscular tissue recovery, but it is not clear whether the effects of MSCs and exercise are additive or synergistic.

A cell-mechanobiological model is used for the prediction of bone density variation in rat tibiae under medium and high mechanical loads. The proposed theoretical-numerical model has only four parameters that need to be identified experimentally. It was used on three groups of male Wistar rats under sedentary, moderate intermittent and continuous running scenarios over an eight week period. The theoretical numerical model was able to predict an increase in bone density under intermittent running (medium intensity mechanical load) and a decrease of bone density under continuous running (higher intensity mechanical load). The numerical predictions were well correlated with the experimental observations of cortical bone thickness variations, and the experimental results of cell activity enabled us to validate the numerical results predictions. The proposed model shows a good capacity to predict bone density variation through medium and high mechanical loads. The mechanobiological balance between osteoblast and osteoclast activity seems to be validated and a foreseen prediction of bone density is made available.

Although the benefits of physical exercise to preserve bone quality are now widely recognized, the intimate mechanisms leading to the underlying cell responses still require further investigations. Interval training running, for instance, appears as a generator of impacts on the skeleton, and particularly on the progenitor cells located in the bone marrow. Therefore, if this kind of stimulus initiates bone cell proliferation and differentiation, the activation of a devoted signaling pathway by mechano-transduction seems likely. This study aimed at investigating the effects of an interval running program on the appearance of the zinc finger protein FHL2 in bone cells and their anatomical location. Twelve 5-week-old male Wistar rats were randomly allocated to one of the following groups (n = 6 per group): sedentary control (SED) or high-intensity interval running (EX, 8 consecutive weeks). FHL2 identification in bone cells was performed by immuno-histochemistry on serial sections of radii. We hypothesized that impacts generated by running could activate, in vivo, a specific signaling pathway, through an integrin-mediated mechano-transductive process, leading to the synthesis of FHL2 in bone marrow cells. Our data demonstrated the systematic appearance of FHL2 (% labeled cells: 7.5%, p < 0.001) in bone marrow obtained from EX rats, whereas no FHL2 was revealed in SED rats. These results suggest that the mechanical impacts generated during high-intensity interval running activate a signaling pathway involving nuclear FHL2, such as that also observed with dexamethasone administration. Consequently, interval running could be proposed as a non-pharmacological strategy to contribute to bone marrow cell osteogenic differentiation.