PMID- 8088924 OWN - NLM STAT- MEDLINE DCOM- 19941019 LR - 20190920 IS - 0360-3997 (Print) IS - 0360-3997 (Linking) VI - 18 IP - 3 DP - 1994 Jun TI - Formation and mineralization of extracellular matrix secreted by an immortal human osteoblastic cell line: modulation by tumor necrosis factor-alpha. PG - 267-84 AB - Tumor necrosis factor-alpha (TNF-alpha), a 17-kDa cytokine produced by stimulated macrophages/monocytes, modulates the functions of a variety of cells and has been shown to induce bone resorption in vitro. However, the effects that TNF-alpha may have on the process of bone formation are not completely understood. In order to study the effects of TNF-alpha on matrix development and mineralization, we utilized a human osteoblastic cell line, HOS TE85. Our results show that HOS TE85, which has been shown to be responsive to hormones active on normal osteoblasts, forms an extensive extracellular matrix (ECM) that mineralizes during extended culture. Treatment during the development of the matrix with TNF-alpha has little effect on cell number and DNA synthesis, showing thereby that TNF-alpha is not cytotoxic to the cells. However, TNF-alpha inhibits the formation of alkaline phosphatase (AP)-positive foci in a dose-dependent manner at concentrations of 0.1-10 ng/ml. TNF-alpha treatment caused a significant decrease in the incorporation of collagen into the developing matrix. In addition, TNF-alpha treatment resulted in a significant decrease in the synthesis of AP by HOS TE85 cells during the process of ECM formation and resulted in a pronounced lack of mineralization of the ECM. These results indicate that TNF-alpha may be acting as an uncoupler by decreasing the synthesis and incorporation of proteins required for bone formation, and inhibiting matrix formation and mineralization in vitro. FAU - Panagakos, F S AU - Panagakos FS AD - Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103. FAU - Hinojosa, L P AU - Hinojosa LP FAU - Kumar, S AU - Kumar S LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Minerals) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-34-5 (Collagen) RN - 9007-49-2 (DNA) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Cell Division/drug effects MH - Cell Line, Transformed MH - Collagen/metabolism MH - DNA/biosynthesis MH - Extracellular Matrix/metabolism/*physiology MH - Humans MH - Minerals/*metabolism MH - Osteoblasts/*metabolism/pathology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1994/06/01 00:00 MHDA- 1994/06/01 00:01 CRDT- 1994/06/01 00:00 PHST- 1994/06/01 00:00 [pubmed] PHST- 1994/06/01 00:01 [medline] PHST- 1994/06/01 00:00 [entrez] AID - 10.1007/BF01534268 [doi] PST - ppublish SO - Inflammation. 1994 Jun;18(3):267-84. doi: 10.1007/BF01534268.