Pyrophosphate therapy prevents trauma-induced calcification in the mouse model of neurogenic heterotopic ossification

J Cell Mol Med. 2020 Oct;24(20):11791-11799. doi: 10.1111/jcmm.15793. Epub 2020 Sep 4.

Abstract

Trauma-induced calcification is the pathological consequence of complex injuries which often affect the central nervous system and other parts of the body simultaneously. We demonstrated by an animal model recapitulating the calcification of the above condition that adrenaline transmits the stress signal of brain injury to the calcifying tissues. We have also found that although the level of plasma pyrophosphate, the endogenous inhibitor of calcification, was normal in calcifying animals, it could not counteract the acute calcification. However, externally added pyrophosphate inhibited calcification even when it was administered after the complex injuries. Our finding suggests a potentially powerful clinical intervention of calcification triggered by polytrauma injuries which has no effective treatment.

Keywords: animal models; bone-brain-nervous system interactions; disorders of calcium/phosphate metabolism; intervention; preclinical studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / pharmacology
  • Animals
  • Brain Injuries, Traumatic / complications*
  • Brain Injuries, Traumatic / pathology
  • Cardiotoxins
  • Diphosphates / blood
  • Diphosphates / therapeutic use*
  • Disease Models, Animal
  • Epinephrine
  • Female
  • Gene Expression Regulation
  • Mice, Inbred C57BL
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Ossification, Heterotopic / blood
  • Ossification, Heterotopic / complications*
  • Ossification, Heterotopic / diagnostic imaging
  • Receptors, Adrenergic / metabolism
  • Vascular Calcification / blood
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / etiology*
  • Vascular Calcification / genetics
  • X-Ray Microtomography

Substances

  • Adrenergic Antagonists
  • Cardiotoxins
  • Diphosphates
  • Receptors, Adrenergic
  • diphosphoric acid
  • Epinephrine