IL-6 receptor expression and IL-6 effects change during osteoblast differentiation.
Studies of the effects of interleukin-6 on osteoblasts have yielded conflicting results. In several earlier in vitro studies it has been stated that IL-6 has no effects on osteoblasts unless soluble IL-6 receptor is added. These results are contradictory to the fact that IL-6 receptors are expressed in osteoblasts in vivo. In this study, MC3T3 preosteoblast cells and rat bone marrow stromal cells were cultured in bone inducing medium containing ascorbic acid, beta-glycerophosphate or dexamethasone. We found that IL-6 receptor expression increased in both types of cells during in vitro differentiation. Furthermore in MC3T3 cells IL-6 decreased proliferation and enhanced expression of two osteoblast-specific differentiation markers, Runx2 and osteocalcin, in proper sequential order. Interestingly, in both cell types IL-6-induced apoptosis only in later culture stages. We also found in MC3T3 cells that IL-6 induced STAT3 activation was significantly higher in later culture stages, i.e. when IL-6 receptor expression was high. The present study shows that IL-6 receptor expression increases during in vitro osteoblast differentiation and that IL-6 functions as a differentiation regulator of preosteoblast cells and an apoptosis initiator in more mature cells.
Department for Clinical Science, Intervention and Technology (CLINTEC), Division of Orthopedics, Karolinska Institute, K54, S-141 86 Huddinge, Sweden. liyan705@hotmail.com
Yan
Y
Li
Carl-Magnus
CM
Bäckesjö
Lars-Arne
LA
Haldosén
Urban
U
Lindgren
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D017077:Culture Media, Conditioned; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor