Signaling pathway STAT1 is strongly activated by IFN-β in the pathogenesis of osteoporosis

Claudine Seeliger*, Lilianna Schyschka, Zienab Kronbach, Angela Wottge, Martijn van Griensven, Britt Wildemann, Helen Vester

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Despite extensive research, the underlying pathological mechanisms of osteoporosis are not completely understood. Recent studies have indicated a distinct role for the IFN-β/STAT1 pathway in bone metabolism. An inhibitory effect of IFN-β on osteoclastogenesis has been detected and STAT1/2 has been shown to influence osteoblastic bone metabolism. So far, no data concerning the IFN-β/STAT1 pathways in osteoblasts and osteoclasts from osteoporotic and non-osteoporotic patients are available. The aim of the study was to analyze these pathways in both cell types.

METHODS: Osteoblasts were isolated from the femoral heads of 12 osteoporotic and 11 non-osteoporotic patients and monocytes were differentiated into osteoclasts. After the differentiation period, cells were stimulated once with 20 and 100 ng/mL IFN-β for 4 days. Viability, activity, bone metabolism-related genes, and the proteins Fra1, SOCS1, STAT1, p-STAT1, and TRAF6 were analyzed.

RESULTS: Viability, activity, and gene expressions were not affected by stimulating the osteoblasts. However, in osteoporotic osteoclasts, which display a significantly higher basal osteoclastic activity, the stimulation with IFN-β lead to significant inhibition. Further, an increased STAT1 activation was detected in both cell types with no significant differences between the groups. Regarding the phosphorylation of STAT1, no significant influence was detected in osteoblasts but the IFN-β stimulation led to a significant increase of p-STAT1 in osteoclasts of both groups.

CONCLUSIONS: IFN-β is a principal mediator in the pathogenesis of osteoporosis by inhibiting osteoclasts and inducing and activating STAT1. Our results also confirm this in cells from osteoporotic and non-osteoporotic patients. Strong inhibitory effects on the osteoclastogenesis of osteoporotic osteoclasts were detectable. Nevertheless, osteoblast activity was not negatively affected by IFN-β stimulation. These results may contribute to a better understanding of the underlying pathological signaling pathways of osteoporosis.

Original languageEnglish
Pages (from-to)1
JournalEuropean Journal of Medical Research
Publication statusPublished - 7 Jan 2015
Externally publishedYes


  • Cells, Cultured
  • Humans
  • Interferon-beta/pharmacology
  • Osteoblasts/drug effects
  • Osteogenesis
  • Osteoporosis/etiology
  • Proto-Oncogene Proteins c-fos/genetics
  • STAT1 Transcription Factor/genetics
  • Signal Transduction
  • TNF Receptor-Associated Factor 6/genetics

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