Abstract
Osteoporosis has become a worldwide disease characterized by a reduction in bone mineral density and the alteration of bone architecture leading to an increased risk of fragility fractures. And an increasing number of studies have indicated that osteoblasts undergo a large number of programmed death events by many different causes in osteoporosis and release NLRP3 and interleukin (e.g., inflammatory factors), which play pivotal roles in contributing to excessive differentiation of osteoclasts and result in exaggerated bone resorption. NLRP3 is activated during pyroptosis and processes the precursors of IL-1β and IL-18 into mature forms, which are released into the extracellular milieu accompanied by cell rupture. All of these compounds are the classical factors of pyroptosis. The cellular effects of pyroptosis are commonly observed in osteoporosis. Although many previous studies have focused on the pathogenesis of these inflammatory factors in osteoporosis, pyroptosis has not been previously evaluated. In this review, pyroptosis is proposed as a novel hypothesis of osteoporosis pathogenesis for the first time, thus providing a new direction for the treatment of osteoporosis in the future.
Highlights
Osteoporosis is a systemic bone metabolism disease with characteristics of microstructural deterioration of bone tissue and decreased bone density
Precursors of IL-1b and IL-18 are processed by caspase-1 during pyroptosis and secreted into the extracellular milieu along with cell debris, which aggravates the inflammatory condition
The formation of osteoclasts exceeds that of osteoblasts, which leads to superfluous bone resorption and an imbalance of bone remodeling, which subsequently results in osteoporosis
Summary
Osteoporosis is a systemic bone metabolism disease with characteristics of microstructural deterioration of bone tissue and decreased bone density. These signaling pathways cause the activation of some transcription factors, such as c-Jun Nterminal kinase (JNK), AP-1, NF-kB, and p38 MAPK [55, 59] It was first reported by S-M Dai et al in 2004 that IL-1 stimulates osteoclastogenesis indirectly through the upregulation of the production of RANKL from rheumatoid arthritis synovial T cells [60]. An observation by S-M Dai showed that IL-18 indirectly stimulated osteoclastic formation through the upregulation of the production of RANKL from T cells, which is as effective as IL-1b but less potent than TNF-a [60]. Jenko B et al showed that at the genetic level, the NLRP3 inflammasome components expressed were significantly higher in patients with RA compared to controls and the NF-kB signaling pathway was upregulated as a result, which facilitates the formation of osteoclasts [98, 99]. In estrogen-deficient osteoporosis, direct bacterial infection was not observed but NLRP3 levels still rose, the viability of osteoblasts was significantly increased, and osteoporosis was relieved when NLRP3 was inhibited or inactivated [112, 113]
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