VSIG4 inhibits RANKL-induced osteoclastogenesis by enhancing Nrf2-dependent antioxidant response against reactive oxygen species production.

Osteoporosis is a prevalent systemic skeletal disorder, particularly affecting postmenopausal women, primarily due to excessive production and activation of osteoclasts. However, the current anti-osteoporotic drugs utilized in clinical practice may lead to certain side effects. Therefore, it is necessary to further unravel the potential mechanisms regulating the osteoclast differentiation and to identify novel targets for osteoporosis treatment. This study revealed the most significant decline in VSIG4 expression among the VSIG family members. VSIG4 overexpression significantly inhibited RANKL-induced osteoclastogenesis and bone resorption function. Mechanistically, both western blot and immunofluorescence assay results demonstrated that VSIG4 overexpression attenuated the expression of osteoclast marker genes and dampened the activation of MAPK and NF-κB signaling pathways. Furthermore, VSIG4 overexpression could inhibit the generation of reactive oxygen species (ROS) and stimulate the expression of Nrf2 along with its downstream antioxidant enzymes via interaction with Keap1. Notably, a potent Nrf2 inhibitor, ML385, could reverse the inhibitory effect of VSIG4 on osteoclast differentiation. In line with these findings, VSIG4 overexpression also mitigated bone loss induced by OVX and attenuated the activation of osteoclasts in vivo. In conclusion, our results suggest that VSIG4 holds promise as a novel target for addressing postmenopausal osteoporosis. This is achieved by suppressing osteoclast formation via enhancing Nrf2-dependent antioxidant response against reactive oxygen species production.

Inhibition of KIF11 ameliorates osteoclastogenesis via regulating mTORC1-mediated NF-κB signaling.

Osteoporosis, characterized by over-production and activation of osteoclasts, has become a major health problem especially in elderly women. In our study, we first tested the effect of Caudatin (Cau) in osteoclastogenesis, which is separated from Cynanchum auriculatum as a species of C-21 steroidal glyosides. The results indicated that Cau suppressed osteoclastogenesis in a time- and dose-dependent manner in vitro. Mechanistically, Cau was identified to inhibit NF-κB signaling pathway via modulation of KIF11-mediated mTORC1 activity. In vivo, by establishing an ovariectomized (OVX) mouse model to mimic osteoporosis, we confirmed that Cau treatment prevented OVX-induced bone loss in mice. In conclusion, we demonstrated that Cau inhibited NF-κB signaling pathway via modulation of KIF11-mediated mTORC1 activity to suppress osteoclast differentiation in vitro as well as OVX-induced bone loss in vivo. This provides the possibility of a novel prospective drug for osteoporosis remedies.

Osteophyte formation causes neurological symptoms after anterior cervical discectomy and fusion (ACDF): A case report.

Spinal surgeons have been drawn to the incidence of osteophytes following intervertebral disc degeneration in clinical practice. However, the production of osteophytes, particularly in the spinal canal, after anterior cervical discectomy and fusion (ACDF) is uncommon. We described a 42-year-old male patient who underwent C4-6 ACDF due to cervical stenosis two years prior in another public hospital in the province. His primary symptoms were significantly relieved, but he developed new pain and weakness in his right leg six months after surgery. The imaging results revealed a large posterior osteophyte at C5/6, compressing the spinal cord anteriorly. Accordingly, we performed cervical open-door laminoplasty to decompress the spinal cord. The patient's clinical symptoms had significantly improved at the one-year follow-up. This case seeks to inform surgeons that cautious, routine follow-ups are necessary for the event that a severe intracanal osteophyte develops at the operated level following ACDF. The comprehensive osteophyte removal and strong fixation at the operative level during ACDF warrant more consideration as these procedures may lower the incidence of new osteophytes. Additionally, surgical procedures may be required.

[Long-term outcome of 52 patients with chronic periaortitis treated with steroids, immunosuppressive therapy and(or) tamoxifen.].

OBJECTIVE: The study aims to assess the therapeutic benefit of medicine treatment in chronic periaortitis. METHOD: A retrospective study of 52 patients with chronic periaortitis treated at Peking Union Medical College Hospital. Summarize clinical features, level of acute-phase reactants, extent of ureteral obstruction, level of renal function, size of mass with repeated follow-up CT scanning during the period of therapy. RESULTS: The most prominent symtom was back or abdominal pain. 76.92% had ureteral obstruction, with 26.92% had a progressive renal failure. After a period of treatment, 95.35% were significant to complete resolution of symptoms. There was also a remarkable decrease in ESR and C-reactive protein a median treatment of 4 weeks. Creatinine decreased significantly (P = 0.002) in patients with progressive renal failure. 66.67% was successfully removed the ureteric stents. CT scanning showed 75% mass regression after a median of 6 months. CONCLUSIONS: The clinical manifestations of chronic periaortitis is nonspecific, which often leads to a delayed diagnosis and the late complications. Chronic periaortitis is very effectively treated by a combination of steroids and immunosuppressive therapy and(or) tamoxifen, with excellent long-term outcome and relatively fewer disease relapse.