Dexamethasone Down-regulates Osteocalcin in Bone Cells through Leptin Pathway

Abstract

Glucocorticoid therapy, especially at higher doses, is associated with significant adverse side effects including osteoporosis. Leptin, secreted from adipose tissue, has diverse effects on bone tissue regulation. As glucocorticoids stimulate leptin synthesis and secretion directly in adipose tissue we hypothesised that dexamethasone (DEX) induced osteoporosis may, in part, be mediated by an osteoblast dependent leptin-leptin receptor pathway. Human bone cells expressed leptin and leptin receptors (Ob-Ra and Ob-Rb). DEX increased leptin, Ob-Ra and Ob-Rb expression in a dose-dependent manner while decreasing expression of osteocalcin. In the presence of leptin, Cbfa1 and osteonectin expression showed no significant change, whereas osteocalcin expression was decreased. Recombinant human quadruple antagonist leptin suppressed DEX-induced osteocalcin downregulation. The signaling pathway involved up-regulation of JAK2. In conclusion, upregulation of leptin and Ob-Rb in human bone cells by DEX is associated with down-regulation of osteocalcin expression. The down regulation of osteocalcin by DEX was partially through a leptin autocrine/paracrine loop. Adverse effects of DEX on the skeleton may be modified by targeting leptin signaling pathways.

Serum Biomarkers Related to Glucocorticoid‐Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case‐Control Study

“…Scholars have long debated the impact of GCs on the expression and circulating level of ADPN . Regarding LEP, it was contradicted to our results that most of the previous studies reported increases LEP levels after GC therapy . These differing findings may be due to the divergent baseline characteristics of patients when they started GC therapy because the underlying diseases are known to influence ADPN and LEP levels.…”

Nitrogen Containing Bisphosphonates Impair the Release of Bone Homeostasis Mediators and Matrix Production by Human Primary Pre-Osteoblasts

“…Between washes, samples were vortexed at high speed to further promote the removal of debris and contaminant tissues. Bone chips were then placed, without any step of enzymatic digestion 22, 23, in 60mm petri dishes and cultured in high glucose DMEM supplemented with 10%FBS (Euroclone, Pero, Italy), 2mM L-glutamine, 50U/ml penicillin and 50μg/ml streptomycin at 37°C in a humidified atmosphere containing 5% CO 2 . Culture media were changed twice a week.…”

Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review

“…These results imply that glial cells which play important in cannabinoid‐mediated pain may also play role in osteoporotic pain through inflammation which is also a common reason for osteoporosis and osteoporotic pain . In addition, it is reported that bone cells also express leptin and leptin receptor which is modulated by glucocorticord and dexamethasone . All these studies suggest that the involvement of the nervous system including glial cells may be another mechanism for cannabinoid to modulate osteoporosis and osteoporotic pain, which remains to be further studied.…”

“…[42] In addition, it is reported that bone cells also express leptin and leptin receptor which is modulated by glucocorticord and dexamethasone. [43] All these studies suggest that the involvement of the nervous system including glial cells may be another mechanism for cannabinoid to modulate osteoporosis and osteoporotic pain, which remains to be further studied.…”