The endocrine disruptor cadmium alters human osteoblast-like Saos-2 cells homeostasis in vitro by alteration of Wnt/β-catenin pathway and activation of caspases.
OBJECTIVE
The pollutant Cadmium (Cd) is widespread in the environment and causes alterations of human health by acting as an endocrine disruptor. Bone tissue seems to be a crucial target of Cd contamination. Indeed, we have previously demonstrated that this endocrine disruptor induces osteoblast apoptosis and necrosis. Thus, aim of this study was to further evaluate the effect of Cd on osteoblasts homeostasis, investigating potential modification of the Wnt/β-catenin intracellular pathway, the intracellular process involved in programmed cellular death and the cytoskeletal alterations.


METHODS
To this purpose, human osteoblastic Saos-2 cells, a human osteosarcoma osteoblast-like cell line, were cultured and treated with Cd.


RESULTS
Osteoblastic cells were treated for 6 h with 10μM Cd, which induced nuclear translocation of β-catenin and increased expression of Wnt/β-catenin target genes. Longer exposure to the same Cd concentration induced osteoblastic cell apoptosis. To better characterize the intracellular events involved in these Cd-induced alterations, we evaluated the effect of Cd exposure on actin filaments and proteins associated to cytoskeletal actin, characterized by the presence of LIM domains. Long (15, 24 h) exposure of osteoblasts to Cd reduced LIM proteins expression and induced actin filaments destruction and a significant caspase-3 activation after 24 h. In addition, to prove that Cd induces osteoblastic cells apoptosis after long exposure, we performed TUNEL assay which demonstrated increase of cell apoptosis after 24 h.


CONCLUSIONS
In conclusion, our study shows that osteoblasts exposed to Cd for short intervals of time demonstrated an increase in cell proliferation through a Wnt/β-catenin dependent mechanism, likely as a compensatory mechanism in response to cell injury. Longer exposure to the same Cd concentration induced cells apoptosis through cytoskeleton disruption-mediated mechanisms and caspase activation.
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.|LiSa Laboratory, Policlinico di Catania, University of Catania, Catania, Italy.
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Papa
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.|LiSa Laboratory, Policlinico di Catania, University of Catania, Catania, Italy.
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Bimonte
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.|LiSa Laboratory, Policlinico di Catania, University of Catania, Catania, Italy.
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Wannenes
Department of Biochemistry, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
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D'Abusco
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.|LiSa Laboratory, Policlinico di Catania, University of Catania, Catania, Italy.
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Fittipaldi
Department of Biochemistry, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
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Scandurra
Department of Biochemistry, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
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Politi
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.
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Crescioli
Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
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Lenzi
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy.
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Di Luigi
Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Largo Lauro De Bosis 15, 00195, Rome, Italy. silvia.migliaccio@uniroma4.it.
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Migliaccio
D008841:Actin Cytoskeleton / Q000187:drug effects*; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D010006:Osteoblasts / Q000187:drug effects*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
D052244:Endocrine Disruptors; D002104:Cadmium
Cadmium; Differentiation; Osteoblasts