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by claude@2026-07, 2026-07-03
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This paper investigated how tetracycline (TC) and three TC derivatives (oxytetracycline, doxycycline, and minocycline) affect osteoclast and osteoblast activities using in vitro human cell models and in vivo zebrafish assays. The study found that all TC derivatives inhibited osteoclast differentiation and bone resorption, with doxycycline showing the strongest inhibitory effects, as measured by reduced TRAP-positive osteoclasts, resorption pit volume, and decreased MMP-2/MMP-9 secretion; low-to-moderate doses also increased osteoblast proliferation and mineralization while high doses suppressed these processes. A limitation explicitly reflected by the experimental design is that it used cell and zebrafish models, which may not fully capture human bone disease physiology. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Osteoporosis is a progressive skeletal disorder characterized by decreased bone mass and an increased risk of fracture. Current treatments are limited by adverse effects and poor long-term compliance, necessitating alternative therapeutic approaches. Tetracycline (TC) derivatives, which are traditionally used as antibiotics, have shown promise in modulating bone remodeling. In this study, the effects of TC and three TC derivatives—oxytetracycline (OC), doxycycline (DC), and minocycline (MC)—on osteoclast and osteoblast activities were investigated using in vitro human cell models and in vivo zebrafish assays. All TC derivatives inhibited osteoclast differentiation and bone resorption, as shown by reductions in the number of TRAP-positive cells, resorption pit volume, and matrix metalloproteinase (MMP)-2/MMP-9 secretion. DC demonstrated the most potent inhibitory effects across all concentrations. Low to moderate concentrations of OC, DC, and MC promoted osteoblast proliferation and mineralization, whereas high doses inhibited these processes. Confocal imaging confirmed the accumulation of TC derivatives in mineralized bone nodules. Zebrafish studies revealed dose-dependent suppression of craniofacial bone development at higher concentrations. These findings highlight the dose dependent, dual effects of TC derivatives on bone cells (osteoblasts and osteoclasts) and underscore the potential of these agents as dual-function therapies for osteoporosis.
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Abstract
Osteoporosis is a progressive skeletal disorder characterized by decreased bone mass and an increased risk of fracture. Current treatments are limited by adverse effects and poor long-term compliance, necessitating alternative therapeutic approaches. Tetracycline (TC) derivatives, which are traditionally used as antibiotics, have shown promise in modulating bone remodeling. In this study, the effects of TC and three TC derivatives—oxytetracycline (OC), doxycycline (DC), and minocycline (MC)—on osteoclast and osteoblast activities were investigated using in vitro human cell models and in vivo zebrafish assays. All TC derivatives inhibited osteoclast differentiation and bone resorption, as shown by reductions in the number of TRAP-positive cells, resorption pit volume, and matrix metalloproteinase (MMP)-2/MMP-9 secretion. DC demonstrated the most potent inhibitory effects across all concentrations. Low to moderate concentrations of OC, DC, and MC promoted osteoblast proliferation and mineralization, whereas high doses inhibited these processes. Confocal imaging confirmed the accumulation of TC derivatives in mineralized bone nodules. Zebrafish studies revealed dose-dependent suppression of craniofacial bone development at higher concentrations. These findings highlight the dose dependent, dual effects of TC derivatives on bone cells (osteoblasts and osteoclasts) and underscore the potential of these agents as dual-function therapies for osteoporosis.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Funding: Sigrid Jusélius Foundation (#230131), the Japan Society for the Promotion of Science (#23K08670), the Murata Science Foundation, the Turku Collegium for Science, Medicine and Technology.
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