Effects of serum from children with newly diagnosed Crohn disease on primary cultures of rat osteoblasts.
OBJECTIVE
We propose that Crohn disease (CD) decreases bone formation via circulating inflammatory mediators. We therefore examined the effects of serum from newly diagnosed, untreated children with CD on osteoblasts in culture and the role of interleukin-6 (IL-6), a cytokine present in excess in active CD that also has direct effects on bone.


METHODS
Bone mineral density was measured by dual x-ray absorptiometry. Primary cultures of rat osteoblasts were treated with serum from patients with CD and healthy controls. We measured expression of osteoblast proliferation, viability, differentiation markers, and mineralized nodule formation. Neutralizing antibodies were used to inhibit the effects of IL-6 present in serum.


RESULTS
We studied 24 children with CD (14 male) and 31 controls (15 male). Spine bone mineral density was lower in patients with CD (Z score, -0.8 +/- 0.9 vs. 0.0 +/- 1.0 for controls; P < 0.05). Nodule formation was markedly decreased in osteoblasts treated with CD serum. However, CD serum did not affect osteoblast proliferation or viability. Expression of proteins characteristic of mature osteoblasts-osteocalcin and alkaline phosphatase-was reduced. Unlike our results in a model of intact bone, neutralization of IL-6 did not inhibit the effects of CD serum. Addition of IL-6 to control serum to match serum concentrations in CD had no effect either.


CONCLUSIONS
CD serum affects osteoblast function and probably differentiation in vitro, suggesting a mechanism by which CD may affect bone formation. IL-6 by itself is not sufficient to cause these effects and probably needs a cofactor present in intact bone.
Varghese
Samuel
S
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut, USA.
Wyzga
Nancy
N
Griffiths
Anne M
AM
Sylvester
Francisco A
FA
D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D016022:Case-Control Studies; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D003424:Crohn Disease / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D010006:Osteoblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015850:Interleukin-6; D015675:Osteocalcin; D000469:Alkaline Phosphatase