Abstract
Azithromycin displays immunomodulatory and anti-inflammatory effects in addition to broad-spectrum antimicrobial activity and is used to treat inflammatory diseases, including respiratory and odontogenic infections. Few studies have reported the effect of azithromycin therapy on bone remodeling processes. The aim of this study was to examine the effects of azithromycin on the osteogenic function of osteoblasts using osteoblast-like MC3T3-E1 cells. Cells were cultured in the presence of 0, 0.1, 1, and 10 µg/mL azithromycin, and cell proliferation and alkaline phosphatase (ALPase) activity were determined. In vitro mineralized nodule formation was detected with alizarin red staining. The expression of collagenous and non-collagenous bone matrix protein was determined using real-time PCR or enzyme-linked immunosorbent assays. In cells cultured with 10 µg/mL azithromycin, the ALPase activity and mineralized nodule formation decreased, while the type I collagen, bone sialoprotein, osteocalcin, and osteopontin mRNA expression as well as osteopontin and phosphorylated osteopontin levels increased. These results suggest that a high azithromycin concentration (10 µg/mL) suppresses mineralized nodule formation by decreasing ALPase activity and increasing osteopontin production, whereas low concentrations (≤l.0 µg/mL) have no effect on osteogenic function in osteoblastic MC3T3-E1 cells.
Highlights
Azithromycin is a macrolide antibiotic that inhibits protein synthesis by binding to the bacterial 50S ribosomal subunit [1]
Tonsillar azithromycin is maintained at higher concentrations than the minimum inhibitory concentration (MIC) required to inhibit pathogenic bacteria responsible for respiratory infections after multiple dose regimens (500 mg/day for 3 consecutive days or 500 mg/day for a day followed by 250 mg/day for 2–5 days) [6]
Azithromycin concentrations of 0.1 and 1 μg/mL did not affect osteoblast cell proliferation at all time points, whereas significantly decreased growth was observed on days 5 and 7 following treatment with 10 μg/mL azithromycin compared with untreated cells (Figure 1)
Summary
Azithromycin is a macrolide antibiotic that inhibits protein synthesis by binding to the bacterial 50S ribosomal subunit [1] It displays immunomodulatory and anti-inflammatory effects in addition to broad-spectrum antimicrobial activity and is used to treat asthma and chronic obstructive pulmonary disease [2] as well as respiratory, urogenital, dermal, dental, and other bacterial infections [3,4]. It extensively penetrates tissues, and its concentrations are sustained after serum concentrations have declined to low levels [5]. Sub-antibiotic azithromycin doses attenuated alveolar bone destruction and improved trabecular microarchitectures in a rat model of experimental periodontitis [17]
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