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Objective: Hypertension disrupts the bone integrity and its repair ability. This study explores the efficiency of a therapy based on the application of mesenchymal stem cells (MSCs) to repair bone defects of spontaneously hypertensive rats (SHR). Methods: First, we evaluated SHR in terms of bone morphometry and differentiation of MSCs into osteoblasts. Then, the effects of the interactions between MSCs from normotensive rats (NTR‐MSCs) cocultured with SHR (SHR‐MSCs) on the osteoblast differentiation of both cell populations were evaluated. Also, bone formation into calvarial defects of SHR treated with NTR‐MSCs was analyzed. Results: Hypertension induced bone loss evidenced by reduced bone morphometric parameters of femurs of SHR compared with NTR as well as decreased osteoblast differentiation of SHR‐MSCs compared with NTR‐MSCs. NTR‐MSCs partially restored the capacity of SHR‐MSCs to differentiate into osteoblasts, while SHR‐MSCs exhibited a slight negative effect on NTR‐MSCs. An enhanced bone repair was observed in defects treated with NTR‐MSCs compared with control, stressing this cell therapy efficacy even in bones damaged by hypertension. Conclusion: The use of MSCs derived from a heathy environment can be in the near future a smart approach to treat bone loss in the context of regenerative dentistry for oral rehabilitation of hypertensive patients. [ABSTRACT FROM AUTHOR]