The Roles Played by Pathogen Recognition Receptors in Pathophysiology of Osteoporosis

Osteoporosis is a complex skeletal disorder marked by reduced bone density and heightened susceptibility to fractures.Although aging, hormonal imbalances, and genetic factors contribute to its development, recent studies suggest that innate immune receptors, particularly pathogen recognition receptors (PRRs), play a pivotal role in its pathophysiology.PRRs, such as toll-like receptors, NOD-like receptors, and RIG-I-like receptors (RLRs), detect microbial components and cellular damage signals, triggering inflammatory responses that disrupt bone remodeling.Activation of NLRP3 inflammasomes, for example, leads to the release of pro-inflammatory cytokines like interleukin (IL)-1β and IL-18, which accelerate bone resorption by promoting osteoclast activity.Similarly, TLR4 signaling enhances RANKL expression, further driving osteoclastogenesis and bone loss.Conversely, experimental studies demonstrate that inhibiting specific PRRs, such as TLR9 or NLRP3, can preserve bone mass by reducing inflammation and restoring osteoblast function.Beyond direct immune-bone interactions, PRRs also mediate crosstalk between gut microbiota and skeletal health, highlighting their systemic influence.This review consolidates current insights into PRR mechanisms in osteoporosis, emphasizing their dual impact on bone formation and resorption.Unraveling these pathways offers potential for innovative therapies targeting PRR-mediated inflammation.Future research should investigate less-studied PRRs, epigenetic influences, and immune-bone cell communication to advance osteoporosis management.