title: HMGB1 expression and release by bone cells.
abstract: Immune and bone cells are functionally coupled by pro-inflammatory cytokine intercellular signaling networks common to both tissues and their crosstalk may contribute to the etiologies of some immune-associated bone pathologies. For example, the receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK) signaling axis plays a critical role in dendritic cell (DC) function as well as bone remodeling. The expression of RANKL by immune cells may contribute to bone loss in periodontitis, arthritis, and multiple myeloma. A recent discovery reveals that DCs release the chromatin protein high mobility group box 1 (HMGB1) as a potent immunomodulatory cytokine mediating the interaction between DCs and T-cells, via HMGB1 binding to the membrane receptor for advanced glycation end products (RAGE). To determine whether osteoblasts or osteoclasts express and/or release HMGB1 into the bone microenvironment, we analyzed tissue, cells, and culture media for the presence of this molecule. Our immunohistochemical and immunocytochemical analyses demonstrate HMGB1 expression in primary osteoblasts and osteoclasts and that both cells express RAGE. HMGB1 is recoverable in the media of primary osteoblast cultures and cultures of isolated osteoclast precursors and osteoclasts. Parathyroid hormone (PTH), a regulator of bone remodeling, attenuates HMGB1 release in cultures of primary osteoblasts and MC3T3-E1 osteoblast-like cells but augments this release in the rat osteosarcoma cell line UMR 106-01, both responses primarily via activation of adenylyl cyclase. PTH-induced HMGB1 discharge by UMR cells exhibits similar release kinetics as reported for activated macrophages. These data confirm the presence of the HMGB1/RAGE signaling axis in bone.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana 46202, USA.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Charoonpatrapong
authors.forename: Rita
authors.initials: R
authors.lastname: Shah
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Robling
authors.forename: Marta
authors.initials: M
authors.lastname: Alvarez
authors.forename: D Wade
authors.initials: DW
authors.lastname: Clapp
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Kopp
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Pavalko
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Bidwell
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology; D001842:Bone and Bones / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000032:analysis / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D024243:HMGB1 Protein; D010281:Parathyroid Hormone; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005576:Colforsin; D000469:Alkaline Phosphatase; D013755:Tetradecanoylphorbol Acetate