Feng Lu1,2, Xinhui Wu3,4, Huiqun Hu1,5, Jiapeng Zhang3,4, Xiaoting Song3,4, Xiangang Jin1,2, Lihua Chen6, Jiacheng Sun3,4, Haixiao Chen7,8,9. 1. Zhejiang University School of Medicine, Hangzhou, 310009, China. 2. Department of Orthopedic, Taizhou Hospital of Zhejiang Province, Zhejiang University, No. 150 Ximen Street, Gucheng Street, Linhai City, Taizhou City, 317000, Zhejiang Province, China. 3. Wenzhou Medical University, Wenzhou, 325035, China. 4. Department of Orthopedic, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317000, China. 5. Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. 6. Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317000, China. 7. Zhejiang University School of Medicine, Hangzhou, 310009, China. xs_luf@enzemed.com. 8. Department of Orthopedic, Taizhou Hospital of Zhejiang Province, Zhejiang University, No. 150 Ximen Street, Gucheng Street, Linhai City, Taizhou City, 317000, Zhejiang Province, China. xs_luf@enzemed.com. 9. Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317000, China. xs_luf@enzemed.com.
Abstract
OBJECTIVES: As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors. METHODS: We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo. RESULTS: Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis. CONCLUSION: Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.
OBJECTIVES: As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors. METHODS: We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo. RESULTS: Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis. CONCLUSION: Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.
Authors: Sara Botto; Daniel N Streblow; Victor DeFilippis; Laura White; Craig N Kreklywich; Patricia P Smith; Patrizia Caposio Journal: Blood Date: 2010-10-07 Impact factor: 22.113
Authors: Azad Alizada; Nadiya Khyzha; Liangxi Wang; Lina Antounians; Xiaoting Chen; Melvin Khor; Minggao Liang; Kumaragurubaran Rathnakumar; Matthew T Weirauch; Alejandra Medina-Rivera; Jason E Fish; Michael D Wilson Journal: Nat Commun Date: 2021-01-25 Impact factor: 14.919