Repurposing sarecycline for osteoinductive therapies: an in vitro and ex vivo assessment.
J Bone Miner Metab
; 41(4): 431-442, 2023 Jul.
Article
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| MEDLINE
| ID: mdl-37036531
ABSTRACT
INTRODUCTION:
Tetracyclines (TCs) embrace a class of broad-spectrum antibiotics with unrelated effects at sub-antimicrobial levels, including an effective anti-inflammatory activity and stimulation of osteogenesis, allowing their repurposing for different clinical applications. Recently, sarecycline (SA)-a new-generation molecule with a narrower antimicrobial spectrum-was clinically approved due to its anti-inflammatory profile and reduced adverse effects verified with prolonged use. Notwithstanding, little is known about its osteogenic potential, previously verified for early generation TCs. MATERIALS ANDMETHODS:
Accordingly, the present study is focused on the assessment of the response of human bone marrow-derived mesenchymal stromal cells (hBMSCs) to a concentration range of SA, addressing the metabolic activity, morphology and osteoblastic differentiation capability, further detailing the modulation of Wnt, Hedgehog, and Notch signaling pathways. In addition, an ex vivo organotypic bone development system was established in the presence of SA and characterized by microtomographic and histochemical analysis.RESULTS:
hBMSCs cultured with SA presented a significantly increased metabolic activity compared to control, with an indistinguishable cell morphology. Moreover, RUNX2 expression was upregulated 2.5-fold, and ALP expression was increased around sevenfold in the presence of SA. Further, GLI2 expression was significantly upregulated, while HEY1 and HNF1A were downregulated, substantiating Hedgehog and Notch signaling pathways' modulation. The ex vivo model developed in the presence of SA presented a significantly enhanced collagen deposition, extended migration areas of osteogenesis, and an increased bone mineral content, substantiating an increased osteogenic development.CONCLUSION:
Summarizing, SA is a promising candidate for drug repurposing within therapies envisaging the enhancement of bone healing/regeneration.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Reposicionamiento de Medicamentos
/
Erizos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Bone Miner Metab
Asunto de la revista:
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Portugal