Tartrate-resistant acid phosphatase augments the bone anabolic response to mechanical loading in male mice

Tartrate-resistant acid phosphatase (TRAP) is an enzyme predominantly expressed in osteoclasts, where it plays a pivotal role in bone remodeling. Deficiency in TRAP leads to severe skeletal impairments such as osteopetrosis in humans and mice. While mechanical loading is known to promote bone mass and growth, the role of TRAP in this adaptive process remains unclear. Here, we applied axial tibial loading and micro-CT analysis to investigate differences in anabolic response to mechanical loading in 16-wk-old male TRAP KO (TRAP^-/-) and WT littermate control mice. In WT mice, mechanical loading enhanced the tibial periosteally enclosed area, trabecular bone volume fraction, trabecular thickness, and trabecular number, indicating a robust anabolic response to mechanical strain. In contrast, TRAP^-/- mice failed to increase cortical bone and displayed markedly reduced trabecular bone formation under the same loading conditions. Analysis of epiphyseal growth plate bony bridges revealed that the number of bridges in lateral tibiae was reduced in TRAP^-/- mice compared to that in WT control mice following mechanical loading, signifying an impaired mechanoadaptive response. Serum alkaline phosphatase concentrations in TRAP-/- mice were similar to those in WT controls, indicating that the inability to respond to mechanical load in TRAP-/- mice is due to TRAP's specific role in the bone's adaptive responses to mechanical loading, possibly involving partially impaired osteoblastic bone formation. These findings highlight TRAP as a mediator of bone adaptation to mechanical loading. Understanding the functions of TRAP in mechanoadaptation could direct therapeutic strategies aimed at improving bone strength and treating conditions associated with TRAP dysfunction.