Elucidating the mechano-molecular dynamics of TRAP activity using CRISPR/Cas9 mediated fluorescent reporter mice.

Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCR) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCR mice exhibited trabecular bone impairments and reduced resorption capacity , RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as C and . These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts . Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCR and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation.