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Cortisol decreases hepatocyte growth factor levels in human osteoblast-like cells
1Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Abstract:
Osteoporosis is a well-known side effect of long-term treatment with glucocorticoids. The hepatocyte growth factor (HGF) receptor is expressed by human osteoclasts and osteoblasts, and mouse osteoblasts also express HGF, indicating that HGF may regulate bone metabolism. Because HGF could be a candidate factor in the local paracrine signaling between osteoblasts and osteoclasts in bone, we decided to study whether human osteoblasts secrete HGF and whether glucocorticoids regulate the expression of HGF. HGF was easily detectable in the culture medium from human osteoblast-like cells (hOB). The HGF protein released into the culture medium was increased with increasing confluency. Hydrocortisone decreased the amount of HGF released into the culture medium from hOB in a dose-dependent manner with a maximal effect at 10(-6) M. Time-course studies revealed that hydrocortisone decreased the amount of HGF released into the culture medium significantly after 16 hours of stimulation (65 +/- 2% of control culture). This effect of hydrocortisone was maximal after 24 hours of stimulation (52 +/- 8% of control culture). In conclusion, HGF is produced by primary cultured hOB cells. Furthermore, the amount of HGF released into the culture medium is decreased by glucocorticoids. The biological significance of this finding remains to be demonstrated.
Insights
Glucocorticoids, used to treat conditions like osteoporosis, reduce the production of hepatocyte growth factor (HGF) by human osteoblasts. This suggests a potential mechanism linking steroid treatment to bone loss.
Area of Science:
- Bone biology
- Endocrinology
- Cell signaling
Background:
- Glucocorticoids are a common cause of osteoporosis.
- Hepatocyte growth factor (HGF) and its receptor are present in bone cells.
- HGF may play a role in bone metabolism and cell communication.
Purpose of the Study:
- To investigate if human osteoblasts secrete HGF.
- To determine if glucocorticoids affect HGF production by osteoblasts.
Main Methods:
- Human osteoblast-like cells (hOB) were cultured.
- HGF levels in the culture medium were measured.
- The effect of hydrocortisone (a glucocorticoid) on HGF release was assessed in a dose- and time-dependent manner.
Main Results:
- Human osteoblasts (hOB) were found to secrete HGF.
- HGF release increased with cell confluency.
- Hydrocortisone significantly decreased HGF release from hOB in a dose-dependent manner, with maximal effect at 10(-6) M.
- Hydrocortisone reduced HGF release by approximately 65% after 16 hours and 52% after 24 hours.
Conclusions:
- Primary cultured human osteoblasts produce and release HGF.
- Glucocorticoids inhibit the release of HGF from human osteoblasts.
- The clinical significance of glucocorticoid-induced HGF reduction in bone metabolism requires further investigation.
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