Dexamethasone-induced lipolysis increases the adverse effect of adipocytes on osteoblasts using cells derived from human mesenchymal stem cells

Dongqing Wang, Azeb Haile, Lynne C Jones

Research output: Contribution to journalArticle

Abstract

The increased bone marrow lipid deposition in steroid-associated bone loss diseases indicates that abnormalities in fat metabolism are associated with disease development. Recent studies have suggested that bone marrow adipocytes are secretory cells and that they may release substances that have an inhibitory effect on the differentiation and function of osteoblasts. We hypothesized that exposure of bone-marrow-derived adipocytes to corticosteroids exacerbates their deleterious effects on osteoblast metabolism and function. Adipocytes and osteoblasts derived from a human mesenchymal stem cell line (240. L) were co-cultured in the absence of direct cell contact with or without dexamethasone treatment. After 6. days of co-culture, osteoblasts demonstrated significantly lower levels of function based on lower mineralization, alkaline phosphatase activity and expression of osteogenic (Runx2, osteocalcin) mRNA marker. Dexamethasone treatment resulted in significantly lower levels of osteoblastic function compared with co-cultured cells without dexamethasone. Furthermore, conditioned media from dexamethasone-treated adipocytes induced a similar toxic effect and increased apoptosis involving activation of caspases 3/7 compared with conditioned media without dexamethasone treatment. Within the conditioned media, a substantial increase in the levels of leptin and two saturated fatty acids (FAs; stearate and palmitate) was observed after dexamethasone treatment. Although leptin supplementation failed to induce the inhibitory effect on osteoblasts, similar toxic results were produced with stearate and palmitate treatment, and an increase in intracellular reactive oxygen species was observed. Stearate- and palmitate-induced apoptosis was blocked by a reactive oxygen species scavenger pyrrolidine dithiocarbamate. These data show that saturated FAs secreted from adipocytes induce lipotoxic effects via mechanisms that may involve reactive oxygen species accumulation in osteoblasts. Our results suggest that inhibition of saturated FA secretion would protect osteoblasts against adipocytes in corticosteroid-associated bone loss diseases.

Original languageEnglish (US)
Pages (from-to)520-530
Number of pages11
JournalBone
Volume53
Issue number2
DOIs
StatePublished - Apr 2013

Fingerprint

Lipolysis
Osteoblasts
Mesenchymal Stromal Cells
Adipocytes
Dexamethasone
Stearates
Palmitates
Conditioned Culture Medium
Reactive Oxygen Species
Poisons
Bone Marrow
Bone Diseases
Leptin
Adrenal Cortex Hormones
Apoptosis
Caspase 7
Osteocalcin
Coculture Techniques
Caspase 3
Alkaline Phosphatase

Keywords

  • Adipocyte
  • Apoptosis
  • Dexamethasone
  • Lipolysis
  • Osteoblast
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Dexamethasone-induced lipolysis increases the adverse effect of adipocytes on osteoblasts using cells derived from human mesenchymal stem cells. / Wang, Dongqing; Haile, Azeb; Jones, Lynne C.

In: Bone, Vol. 53, No. 2, 04.2013, p. 520-530.

Research output: Contribution to journalArticle

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