Localization of Osteoprotegerin (OPG) on Bone Surfaces and Cement Lines in Rat Tibia

Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor family, is an osteoclastogenesis inhibitory factor. We investigated the localization of OPG in rat tibia using a specific peptide antibody to clarify the role of OPG in bone remodeling. OPG reactivity was mainly seen on bone surfaces. In bone matrices, OPG was also localized on cartilage/bone interfaces and cement lines. However, labeling was scarcely detected in the region of contact between osteoclasts and stromal cells. Some osteoblasts and osteocytes showed weak labeling. Immunoreactivity was not seen in chondrocytes or osteoclasts. Immunoelectron microscopic observation revealed that OPG is localized on the bone surfaces under osteoclasts. These findings suggest that OPG derived from osteoblast lineage cells and/or serum may be concentrated on resorbed bone surfaces and subsequently on cement lines. OPG may play an important role in the prevention of excess bone resorption by inhibiting differentiation and activity of osteoclasts in bone remodeling.

[1]  A. Nanci,et al.  High-resolution Immunocytochemistry of Noncollagenous Matrix Proteins in Rat Mandibles Processed with Microwave Irradiation , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  K. Hirokawa,et al.  Expression Profiles of Receptor Activator of Nuclear Factor κB Ligand, Receptor Activator of Nuclear Factor κB, and Osteoprotegerin Messenger RNA in Aged and Ovariectomized Rat Bones , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  J. Williams,et al.  Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane. , 2001, Bone.

[4]  T. Nakashima,et al.  Force‐Induced Osteoclast Apoptosis In Vivo Is Accompanied by Elevation in Transforming Growth Factor β and Osteoprotegerin Expression , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  T. Martin,et al.  Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. , 2000, Endocrinology.

[6]  P. Kostenuik,et al.  Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis , 2000, The Journal of experimental medicine.

[7]  S. Chandrasekhar,et al.  In Vivo Demonstration that Human Parathyroid Hormone 1–38 Inhibits the Expression of Osteoprotegerin in Bone with the Kinetics of an Immediate Early Gene , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  Sundeep Khosla,et al.  The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  A. Bronckers,et al.  Blood Circulation as Source for Osteopontin in Acellular Extrinsic Fiber Cementum and Other Mineralizing Tissues , 1999, Journal of dental research.

[10]  D. Lacey,et al.  Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. , 1999, Endocrinology.

[11]  A. Nanci,et al.  Content and distribution of noncollagenous matrix proteins in bone and cementum: relationship to speed of formation and collagen packing density. , 1999, Journal of structural biology.

[12]  K. Ikeda,et al.  Immunological Characterization of Circulating Osteoprotegerin/Osteoclastogenesis Inhibitory Factor: Increased Serum Concentrations in Postmenopausal Women with Osteoporosis , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  S. Morony,et al.  Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  N. Udagawa,et al.  A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. , 1999, Biochemical and biophysical research communications.

[15]  N. Nagata,et al.  Transforming Growth Factor-β1 Increases mRNA Levels of Osteoclastogenesis Inhibitory Factor in Osteoblastic/Stromal Cells and Inhibits the Survival of Murine Osteoclast-like Cells , 1998 .

[16]  M. Kumegawa,et al.  Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts. , 1998, Biochemical and biophysical research communications.

[17]  B. Riggs,et al.  Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. , 1998, Biochemical and biophysical research communications.

[18]  S. Mochizuki,et al.  Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast. , 1998, Biochemical and biophysical research communications.

[19]  S. Mochizuki,et al.  Hypocalcemic Effect of Osteoclastogenesis Inhibitory Factor/Osteoprotegerin in the Thyroparathyroidectomized Rat. , 1998, Endocrinology.

[20]  B. Kwon,et al.  TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  K Yano,et al.  Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. , 1998, Biochemical and biophysical research communications.

[22]  S. Morony,et al.  osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. , 1998, Genes & development.

[23]  D. Lacey,et al.  Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation , 1998, Cell.

[24]  K Yano,et al.  Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Mochizuki,et al.  Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. , 1998, Endocrinology.

[26]  M. Goto,et al.  Characterization of Structural Domains of Human Osteoclastogenesis Inhibitory Factor* , 1998, The Journal of Biological Chemistry.

[27]  N. Udagawa,et al.  An Ultrastructural Study of Cell-Cell Contact between Mouse Spleen Cells and Calvaria-Derived Osteoblastic Cells in a Co-Culture System for Osteoclast Formation , 1997 .

[28]  S. Mochizuki,et al.  Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. , 1997, Biochemical and biophysical research communications.

[29]  G Shimamoto,et al.  Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density , 1997, Cell.

[30]  M. McKee,et al.  Osteopontin and the Bone Remodeling Sequence , 1995, Annals of the New York Academy of Sciences.

[31]  H. Ozawa,et al.  Immunohistochemical localization of heparan sulfate proteoglycan in rat tibiae , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  M. McKee,et al.  Ultrastructural immunolocalization of noncollagenous (osteopontin and osteocalcin) and plasma (albumin and α2HS‐glycoprotein) proteins in rat bone , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  H. Ozawa,et al.  Characteristic localization of carbohydrates in osteoclasts by lectin cytochemistry. , 1992, Bone.

[34]  T. Martin,et al.  Modulation of osteoclast differentiation. , 1992, Endocrine reviews.

[35]  G. Rodan,et al.  Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. , 1991, The Journal of clinical investigation.

[36]  入江 一元.  Relationships between tooth eruption, occlusion and alveolar bone resorption , 1990 .

[37]  T. Martin,et al.  The bone marrow-derived stromal cell lines MC3T3-G2/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells. , 1989, Endocrinology.

[38]  T. Martin,et al.  Osteoblastic cells are involved in osteoclast formation. , 1988, Endocrinology.

[39]  D. Burr,et al.  Morphology of the osteonal cement line in human bone , 1987, The Anatomical record.

[40]  E H Burger,et al.  Cells of bone: proliferation, differentiation, and hormonal regulation. , 1986, Physiological reviews.

[41]  S. Ejiri,et al.  The preosteoclast and its cytodifferentiation into the osteoclast: ultrastructural and histochemical studies of rat fetal parietal bone. , 1983, Archivum histologicum Japonicum = Nihon soshikigaku kiroku.