Melatonin protects bone against cadmium-induced toxicity via activation of Wnt/β-catenin signaling pathway

Abstract

Among heavy metals, cadmium (Cd) is one of the most toxic for health due to it accumulation in several tissues including bone. Since melatonin (MLT) favors new bone formation through several pathways including Wnt/β-catenin, here we assessed whether MLT has a protective role against Cd induced toxicity in the rat bone tissue. Adult male Wistar rats receiving 50 mg CdCl₂/L and/or 3 mg/L MLT were used and were sacrificed 30 days after the treatment. Femurs and plasma were collected and analyzed by various biochemicals, molecular and histological investigation. The results showed that Cd exposure induced bone disorder characterized by histopathological alterations, a decreased alkaline phosphatase activity and plasmatic concentration of osteocalcin. Moreover, also the expression levels of some osteogenic-related genes (Runx2, Ocn and Alp) were down-regulated after Cd treatment. Since mechanistically Cd toxicity reduced the Kinase activity of GSK3β and protein levels of Wnt3a and β-catenin, we observed that MLT administration significantly ameliorated the toxic effects induced by the metal. Our findings provide clues about a potential protective effect of MLT against Cd-induced bone metabolism destruction and that the protection was partially mediated via the Wnt/β-catenin signaling pathway.

Keywords:

• Cadmium
• bone
• melatonin
• Wnt/β-catenin signaling
• protection

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Latifa Knani

Dr Latifa Knani: Designed and performed experiments, analyzed data and co-wrote the paper.

Massimo Venditti

Dr. Massimo Venditti: Performed western blot and immunofluorescence analyses.

Safa Kechiche

Dr. Safa Kechiche: Contributed to animal experiments and samples collection.

Mohamed Banni

Pr. Mohamed Banni: Performed quantitative real time PCR analyses and provided critical revision of the article.

Imed Messaoudi

Pr. Imed Messaoudi: Designed experiments and co-wrote the paper.

Sergio Minucci

Pr. Sergio Minucci: Supervised the research and provided final approval of the version to submit.