Bone resorption and mRNA expression of IL-6 and IL-6 receptor in patients with renal osteodystrophy.
The cytokine interleukin-6 (IL-6) is a major cell regulatory factor that may play an important role in the bone remodeling of patients with renal failure. IL-6 exerts its action by binding to its receptor (IL-6R), which leads to transduction of a second messenger cascade within cells. In vitro as well as in vivo data point to IL-6 as an autocrine/paracrine factor in bone osteoclasts. Recently, bone cells from patients with Paget's disease were found to express IL-6 and IL-6R mRNA transcripts. However, in patients with renal bone disease, there is currently no in vivo evidence that osteoclasts have the capability to express mRNA for IL-6 and IL-6R. To investigate the potential expression of IL-6 and IL-6R in bone and its relationship to bone cell activity, iliac crest bone biopsies were performed in patients on chronic maintenance dialysis. Messenger RNA expression of IL-6 and IL-6R was studied using in situ hybridization histochemistry, and parameters of bone turnover were determined by bone histomorphometry. In the samples studied, mRNA expression of IL-6 and IL-6R was found in osteoclasts and bone marrow cells. Furthermore, we report the novel finding of increased IL-6R mRNA expression in osteoclasts engaged in increased bone resorption. The results of the present study suggest that the cytokine IL-6 is intricately involved in osteoclastic bone resorption and that expression of its receptor, IL-6R, in osteoclasts may parallel osteoclastic bone resorbing activity.
Langub
M C
MC
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, USA.
Koszewski
N J
NJ
Turner
H V
HV
Monier-Faugere
M C
MC
Geng
Z
Z
Malluche
H H
HH
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001862:Bone Resorption / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics* / Q000502:physiology; D019947:Receptors, Interleukin-6
D015703:Antigens, CD; D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6