Increased mRNA expression and protein secretion of interleukin-6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone

We have investigated the expression and synthesis of potential bone-resorbi ng cytokines, interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosi s factor (TNF) in rheumatoid arthritic (RA) and osteoarthritic (OA) bone, t wo common diseases which are associated with bone loss. Primary human osteo blast (hOB) cultures were established to determine the temporal mRNA expres sion of IL-6, IL-1 (alpha and beta), and TNF (alpha and beta) in relation t o 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 (1 0 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 refl ected by decreasing collagen I (<alpha>(1)), osteopontin, bone sialoprotein , alkaline phosphatase mRNA levels, while osteocalcin (OC) mRNA levels incr eased. 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(<alpha> and b eta) and TNF(alpha and beta) nor the related proteins were detectable. Thes e results indicate that differentiated OA hOB and RA hOB within a bone tiss ue-like matrix constitutively express and secrete high levels of IL-6. This inherent property suggests that these osteoblasts, independent of local in flammatory parameters, can contribute to enhanced recruitment of osteoclast progenitors and thereby bone resorption. J. Cell. Biochem. 81:666-678, 200 1. (C) 2001 Wiley-Liss, Inc.