Bone resorption by aryl hydrocarbon receptor-expressing osteoclasts is not disturbed by TCDD in short-term cultures.
Polychlorinated dibenzo-p-dioxins (PCDDs) are highly toxic environmental contaminants, and 2,3,7,8-tetrachlorobenzo-p-dioxin (TCDD) is the most potent dioxin. Dioxins bind specifically to the cytosolic aryl hydrocarbon receptor (AHR), which is a ligand-activated transcription factor, and a majority of toxic effects of dioxins are mediated via AHR. We have recently demonstrated that TCDD disrupts bone modeling and decreases bone mechanical strength, and that partial resistance to these effects is related to an altered transactivation domain in AHR structure. In order to better understand the effects of dioxins on bone, we studied the presence and precise localization of AHR and also the number and activity of osteoclasts after TCDD treatments. Total RNA was extracted from mixed bone cell population cultures and expression of AHR mRNA was studied using RT-PCR. Bone cells expressed a considerable amount of AHR mRNA. To see which bone cells express AHR, immunostainings were performed in primary rat bone cell cultures, pure human osteoclast cultures and histological sections from AHR knockout and wild type bones. Immunostaining revealed a strong expression of AHR both in osteoclasts and osteoblasts with an especially prominent stain in bone resorbing osteoclasts. Effects of dioxin on primary bone cells were evaluated after TCDD treatment in the pit formation assay. The activity of osteoclasts was not affected measured as the percentage of active osteoclasts and the actual area of resorbed bone. These data indicate that even though TCDD-treated bones show decreased mechanical strength and size, this is not a direct result from increased osteoclastic bone resorption.
Ilvesaro
Joanna
J
Department of Anatomy and Cell Biology, FIN-90014 University of Oulu, Finland.
Pohjanvirta
Raimo
R
Tuomisto
Jouko
J
Viluksela
Matti
M
Tuukkanen
Juha
J
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon