Propofol promotes osteoclastic bone resorption by increasing DC-STAMP expression
김은정, 김형준, 백승완, 김경훈, 류시정, 김철홍, 신상욱,
소속 상세정보
김은정 ( Kim Eun-Jung ) - Pusan National University School of Dentistry Department of Dental Anesthesia and Pain Medicine
김형준 ( Kim Hyung-Joon ) - Pusan National University School of Dentistry Department of Oral Physiology
백승완 ( Baik Seong-Wan ) - Pusan National University School of Medicine Department of Anesthesia and Pain Medicine
김경훈 ( Kim Kyung-Hoon ) - Pusan National University School of Medicine Department of Anesthesia and Pain Medicine
류시정 ( Ryu Sie-Jeong ) - Kosin University College of Medicine Department of Anesthesiology and Pain Medicine
김철홍 ( Kim Cheul-Hong ) - Pusan National University School of Dentistry Department of Dental Anesthesia and Pain Medicine
신상욱 ( Shin Sang-Wook ) - Pusan National University School of Medicine Department of Anesthesia and Pain Medicine
Abstract
Background: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to α-tocopherol. It has been reported that α-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs).
Methods: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol (0?50 μM) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion.
Results: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP.
Conclusion: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.
키워드
Bone Resorption; Cell Fusion; Osteoclasts; Propofol; p38 MAP Kinase
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