TGF-β1 plays a protective role in glucocorticoid-induced dystrophic calcification

La Li, Shiqi Xiang, Bing Wang, Hang Lin, Shinsuke Kihara, Hui Sun, Peter G. Alexander, Rocky S. Tuan

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Dystrophic calcification (DC) is the deposition of calcium in degenerated tissue which occurs as a reaction to tissue damage. Sometimes if tissue repair fails, it can progress into heterotopic ossification (HO), a pathological condition of abnormal bone formation. HO happens frequently in severe trauma patients such as in blast injury, central nervous system injury and burn injury, in which excessive endogenous glucocorticoid production has always been found. Glucocorticoids have a big impact on bone and muscle. However, few studies have investigated the impact of glucocorticoids on DC/HO formation in muscle. This study aimed to determine the role of glucocorticoids in DC/HO pathogenesis following muscular injury and the possible underlying mechanism. In this study, we administered a high dose of a synthetic glucocorticoid, dexamethasone (DEX), to animals with muscle injury induced by cardiotoxin (CTX) injection to mimic a glucocorticoid excess state following severe muscle trauma. The findings reported here showed that DEX treatment together with CTX-induced muscle injury led to a significant amount of DC in muscle. This effect was likely related to protein level alterations in the fibrinolytic system and resultant decreased circulating transforming growth factor-beta 1 (TGF-β1), given that supplementation of recombinant TGF-β1 markedly rescued this phenomenon. In summary, our results suggest that glucocorticoid excess impairs muscle regeneration and promotes DC/HO, and that TGF-β1 could be a key factor in modulating this process.

Original languageEnglish (US)
Article number115355
JournalBone
Volume136
DOIs
StatePublished - Jul 2020

Keywords

  • Dystrophic calcification
  • Glucocorticoid
  • Heterotopic ossification
  • Muscle-derived stromal cells
  • Transforming growth factor-beta 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Li, L., Xiang, S., Wang, B., Lin, H., Kihara, S., Sun, H., Alexander, P. G., & Tuan, R. S. (2020). TGF-β1 plays a protective role in glucocorticoid-induced dystrophic calcification. Bone, 136, [115355]. https://doi.org/10.1016/j.bone.2020.115355