The role of Lactobacillus rhamnosus in improving estrogen deficiency-induced osteoporosis by inhibiting NLRP3 inflammasome activation

Osteoporosis is common in individuals with estrogen deficiency, and current treatments are often accompanied by adverse effects, highlighting the need for safer and more effective therapeutic strategies. This study investigates the protective effects and underlying mechanisms of the probiotic Lactobacillus rhamnosus (LGG) on estrogen deficiency-induced osteoporosis. An ovariectomized (OVX) mouse model of osteoporosis was established and treated with LGG for 8 weeks. Bone structure, NLRP3 inflammasome activation, and bone metabolism were assessed using micro-CT, histological analysis, immunofluorescence, qRT-PCR, and ELISA. In vitro, RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) was performed to examine the effects of LGG on osteoclast formation and NLRP3 activation. LGG improved bone structure in OVX mice, increasing bone microarchitectural parameters such as BV/TV, Tb·Th, and Tb·N, and reduced both the number of osteoclasts and the expression of related molecules. It also decreased the levels of NLRP3 and its downstream targets Caspase-1, IL-1β, and IL-18 in bone tissue, as well as serum bone metabolic markers. In vitro, LGG inhibited RANKL-induced osteoclast differentiation and NLRP3 activation, and this effect was partially reversed by an NLRP3 agonist. LGG alleviates bone loss by suppressing NLRP3 inflammasome activation, offering a new strategy for the prevention and treatment of postmenopausal osteoporosis.