Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression

  • Inflammopharmacology. 2022 Aug;30(4):1445-1458. doi: 10.1007/s10787-022-00985-1.
Feng Lu  1  2 ,  Xinhui Wu  3  4 ,  Huiqun Hu  1  5 ,  Jiapeng Zhang  3  4 ,  Xiaoting Song  3  4 ,  Xiangang Jin  1  2 ,  Lihua Chen  6 ,  Jiacheng Sun  3  4 ,  Haixiao Chen  7  8  9
Affiliations
  • 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. [email protected].
  • 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. [email protected].
  • 9. Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317000, China. [email protected].
PMID: 35451724 DOI: 10.1007/s10787-022-00985-1
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.

Keywords
Chronic inflammation; LPS; Osteoclasts; Osteoporosis; RANKL; Yangonin.
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