A Low Concentration of Citreoviridin Prevents Both Intracellular Calcium Deposition in Vascular Smooth Muscle Cell and Osteoclast Activation In Vitro

Molecules. 2023 Feb 10;28(4):1693. doi: 10.3390/molecules28041693.

Abstract

Vascular calcification (VC) and osteoporosis are age-related diseases and significant risk factors for the mortality of elderly. VC and osteoporosis may share common risk factors such as renin-angiotensin system (RAS)-related hypertension. In fact, inhibitors of RAS pathway, such as angiotensin type 1 receptor blockers (ARBs), improved both vascular calcification and hip fracture in elderly. However, a sex-dependent discrepancy in the responsiveness to ARB treatment in hip fracture was observed, possibly due to the estrogen deficiency in older women, suggesting that blocking the angiotensin signaling pathway may not be effective to suppress bone resorption, especially if an individual has underlying osteoclast activating conditions such as estrogen deficiency. Therefore, it has its own significance to find alternative modality for inhibiting both vascular calcification and osteoporosis by directly targeting osteoclast activation to circumvent the shortcoming of ARBs in preventing bone resorption in estrogen deficient individuals. In the present study, a natural compound library was screened to find chemical agents that are effective in preventing both calcium deposition in vascular smooth muscle cells (vSMCs) and activation of osteoclast using experimental methods such as Alizarin red staining and Tartrate-resistant acid phosphatase staining. According to our data, citreoviridin (CIT) has both an anti-VC effect and anti-osteoclastic effect in vSMCs and in Raw 264.7 cells, respectively, suggesting its potential as an effective therapeutic agent for both VC and osteoporosis.

Keywords: citreoviridin; osteoporosis; vascular calcification.

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Aurovertins* / pharmacology
  • Bone Resorption* / metabolism
  • Calcium / metabolism
  • Estrogens / pharmacology
  • Humans
  • Mice
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Osteoporosis* / metabolism
  • RAW 264.7 Cells
  • Vascular Calcification* / metabolism

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Calcium
  • citreoviridin
  • Estrogens
  • Aurovertins