title: Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells.
abstract: To test the hypothesis that mononuclear cells are stimulated to release interleukin 1 (IL-1) by bone fragments released in the bone microenvironment during the remodeling cycle, we have investigated the effects of bone matrix and some of its constituents on IL-1 secretin from peripheral blood mononuclear cells (PBMC). Increases in IL-1 activity were observed when either PBMC or adherent monocytes, but not lymphocytes depleted of monocytes, were co-cultured with either human or rat bone particles but not with latex particles of similar size. Co-culture of PBMC with bone particles in a transwell system where the cells were physically separated from the bone particles, or with osteoblast- or osteoclast-covered bone particles, did not stimulate IL-1 release, indicating that a physical contact between PBMC and the bone surface is required for eliciting IL-1 release. This was confirmed by the finding of a lower stimulatory effect of bone particles pretreated with etidronate, a bisphosphonate which decreases the bone binding capacity of PBMC. Constituents of bone matrix, such as collagen fragments, hydroxyproline, and, to a lesser extent, transforming growth factor-beta, but not osteocalcin, alpha 2HS glycoprotein, fragments of either bone sialoprotein or osteopontin, and fibronectin, stimulated PBMC IL-1 release in a dose-dependent fashion. Collagen-stimulated IL-1 release was partially and specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1-integrin cell surface collagen receptor. These data demonstrate that products of bone resorption, known to be chemotactic for mononuclear cells, stimulate PBMC IL-1 activity. These findings may help explain previous documentation of increased IL-1 secretion by circulating monocytes obtained from patients with high turnover osteoporosis.
authors.affiliation: Division of Bone and Mineral Metabolism, Washington University School of Medicine and Medical Center, St. Louis, Missouri.
authors.forename: R
authors.initials: R
authors.lastname: Pacifici
authors.forename: A
authors.initials: A
authors.lastname: Carano
authors.forename: S A
authors.initials: SA
authors.lastname: Santoro
authors.forename: L
authors.initials: L
authors.lastname: Rifas
authors.forename: J J
authors.initials: JJ
authors.lastname: Jeffrey
authors.forename: J D
authors.initials: JD
authors.lastname: Malone
authors.forename: R
authors.initials: R
authors.lastname: McCracken
authors.forename: L V
authors.initials: LV
authors.lastname: Avioli
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001857:Bone Matrix / Q000502:physiology*; D001862:Bone Resorption; D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D017886:Durapatite; D012968:Etidronic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D006882:Hydroxyapatites / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D038981:Receptors, Collagen
chemical_list: D000911:Antibodies, Monoclonal; D006882:Hydroxyapatites; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D003094:Collagen; D017886:Durapatite; D011112:Polymyxin B; D012968:Etidronic Acid