1. Dioxins interfere with differentiation of osteoblasts and osteoclasts
- Author
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Elise Kallio, Anu Olkku, Merja Korkalainen, Joanna Ilvesaro, Juha Tuukkanen, Matti Viluksela, Katri Nelo, and Anitta Mahonen
- Subjects
Male ,musculoskeletal diseases ,endocrine system ,medicine.medical_specialty ,Polychlorinated Dibenzodioxins ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Osteocalcin ,Osteoclasts ,Bone Marrow Cells ,Core Binding Factor Alpha 1 Subunit ,Biology ,Dioxins ,Rats, Sprague-Dawley ,Mice ,Osteoclast ,Internal medicine ,medicine ,Animals ,heterocyclic compounds ,Cells, Cultured ,reproductive and urinary physiology ,Bone growth ,Osteoblasts ,Reverse Transcriptase Polymerase Chain Reaction ,Stem Cells ,Bone Marrow Stem Cell ,Cell Differentiation ,Osteoblast ,Alkaline Phosphatase ,Rats ,Mice, Inbred C57BL ,stomatognathic diseases ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Alkaline phosphatase ,Environmental Pollutants ,Bone marrow ,Stem cell - Abstract
We have previously shown that the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone growth, modelling and mechanical strength in vivo. In this study, we utilized differentiation of bone marrow stem cells to osteoblasts and osteoclasts as a model system to study the effects of TCDD on bones. Stem cells were isolated from bone marrow of femurs and tibias of rats and mice. Progress of osteoblastic differentiation was monitored by measuring mRNA expression levels of differentiation markers from control and TCDD-treated cells using quantitative RT-PCR. TCDD significantly and dose-dependently decreased the mRNA levels of RUNX2, alkaline phosphatase and osteocalcin. Also the activity of alkaline phosphatase was significantly inhibited in both rat and mice cells. In the case of osteoclasts, TCDD decreased the number of TRACP+ multinucleated cells, with corresponding decreases in the number of F-actin rings and the area of resorption. Studies in AHR-knockout mice indicated that TCDD has no effect on the expression of osteoblastic differentiation markers suggesting that TCDD mediates its effects by AHR. Both osteoblastic and osteoclastic effects took place at very low doses of TCDD, as in most cases 100 fM TCDD was enough to significantly affect the differentiation markers. Therefore, differentiation of osteoblasts and osteoclasts from bone marrow stem cells seems to be a very sensitive target for TCDD. Disrupting effects in osteoblastic cells, in addition to disturbed osteoclastogenesis, may thus play a role in adverse effects on bone quality in TCDD exposed animals.
- Published
- 2009