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Increased mRNA expression and protein secretion of interleukin‐6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone
Author(s) -
Chenoufi HennaLise,
Diamant Marcus,
Rieneck Klaus,
Lund Bjarne,
Stein Gary S.,
Lian Jane B.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1104
Subject(s) - bone sialoprotein , osteoblast , osteopontin , osteocalcin , endocrinology , runx2 , osteoprotegerin , medicine , messenger rna , bone resorption , alkaline phosphatase , osteoclast , interleukin , tumor necrosis factor alpha , chemistry , biology , cytokine , in vitro , activator (genetics) , gene , receptor , biochemistry , enzyme
We have investigated the expression and synthesis of potential bone‐resorbing cytokines, interleukin‐6 (IL‐6), interleukin‐1 (IL‐1), and tumor necrosis factor (TNF) in rheumatoid arthritic (RA) and osteoarthritic (OA) bone, two common diseases which are associated with bone loss. Primary human osteoblast (hOB) cultures were established to determine the temporal mRNA expression of IL‐6, IL‐1 (α and β), and TNF (α and β) in relation to osteoblast growth and phenotypic genes. IL‐6 mRNA levels were found to be significantly higher ( P < 0.04) in both OA hOB (17 patients) and RA hOB (10 patients) compared to normal (NO) hOB (9 patients) and reached five‐fold increases in OA hOB and 13‐fold increases in RA hOB. Maximal levels of IL‐6 are expressed at Day 21 which corresponds to the mineralization stage reflected by decreasing collagen I (α 1 ), osteopontin, bone sialoprotein, alkaline phosphatase mRNA levels, while osteocalcin (OC) mRNA levels increased. IL‐6 protein levels also were significantly higher ( P < 0.05) in OA hOB and RA hOB compared to NO hOB. These increases were not attributable to sex or age of the donor bone. Neither the mRNA encoding IL‐1(α and β) and TNF(α and β) nor the related proteins were detectable. These results indicate that differentiated OA hOB and RA hOB within a bone tissue‐like matrix constitutively express and secrete high levels of IL‐6. This inherent property suggests that these osteoblasts, independent of local inflammatory parameters, can contribute to enhanced recruitment of osteoclast progenitors and thereby bone resorption. J. Cell. Biochem. 81: 666–678, 2001. © 2001 Wiley‐Liss, Inc.