Endocrine modulation of Brucella abortus-infected osteocytes function and osteoclastogenesis via modulation of RANKL/OPG

Microbes Infect. 2019 Aug-Sep;21(7):287-295. doi: 10.1016/j.micinf.2019.01.004. Epub 2019 Feb 5.

Abstract

Osteoarticular brucellosis is the most frequent complication of active disease. A large amount of cells in bone are osteocytes. Since bone remodeling process is regulated by hormones we sought to study the effect of cortisol and DHEA in Brucella abortus-infected osteocytes. Cortisol treatment inhibited the expression of IL-6, TNF-α, MMP-2 and RANKL in B. abortus-infected osteocytes. DHEA could reverse the inhibitory effect of cortisol on MMP-2 production. B. abortus infection inhibited connexin 43 (Cx43) expression in osteocytes. This expression was increased when cortisol was incorporated during the infection and DHEA treatment partially reversed the effect of cortisol. Osteocytes-infected with B. abortus induced osteoclast's differentiation. Yet, the presence of cortisol, but not DHEA, during osteocyte infection inhibited osteoclastogenesis. Glucocorticoid receptor (GR) is implicated in the signaling of cortisol. Infection with B. abortus was able to increase GRα/β ratio. Levels of intracellular cortisol are not only dependent on GR expression but also a result of the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (11β-HSD)-1 (cortisone to cortisol conversion), 11β-HSD2 (cortisol to cortisone conversion). B. abortus infection increased 11β-HSD 1/2 ratio and cortisone mimicked the effect of cortisol. Our results indicated that cortisol and DHEA could modulate osteocyte responses during B. abortus infection.

Keywords: Adrenal steroids; Brucella abortus; Osteocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases / genetics
  • Animals
  • Brucella abortus / growth & development
  • Brucella abortus / metabolism
  • Brucella abortus / physiology*
  • Brucellosis / metabolism
  • Brucellosis / pathology*
  • Cells, Cultured
  • Connexin 43 / metabolism
  • Cortisone / pharmacology
  • Culture Media, Conditioned / pharmacology
  • Cytokines / metabolism
  • Dehydroepiandrosterone / pharmacology
  • Hydrocortisone / metabolism
  • Hydrocortisone / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Microbial Viability
  • Osteocytes / cytology
  • Osteocytes / drug effects
  • Osteocytes / metabolism
  • Osteocytes / microbiology*
  • Osteogenesis / drug effects
  • Osteoprotegerin / antagonists & inhibitors
  • Osteoprotegerin / metabolism*
  • RANK Ligand / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Signal Transduction

Substances

  • Connexin 43
  • Culture Media, Conditioned
  • Cytokines
  • GJA1 protein, mouse
  • Osteoprotegerin
  • RANK Ligand
  • Receptors, Glucocorticoid
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Dehydroepiandrosterone
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Matrix Metalloproteinase 2
  • Cortisone
  • Hydrocortisone