Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo

@article{citeulike:2973294, abstract = {Resident macrophages are an integral component of many tissues and are important in homeostasis and repair. This study examines the contribution of resident tissue macrophages to bone physiology. Using immunohistochemistry, we showed that a discrete population of resident macrophages, OsteoMacs, was intercalated throughout murine and human osteal tissues. OsteoMacs were distributed among other bone lining cells within both endosteum and periosteum. Furthermore, OsteoMacs were coisolated with osteoblasts in murine bone explant and calvarial preparations. OsteoMacs made up 15.9\% of calvarial preparations and persisted throughout standard osteoblast differentiation cultures. Contrary to previous studies, we showed that it was OsteoMacs and not osteoblasts within these preparations that responded to pathophysiological concentrations of LPS by secreting TNF. Removal of OsteoMacs from calvarial cultures significantly decreased osteocalcin mRNA induction and osteoblast mineralization in vitro. In a Transwell coculture system of enriched osteoblasts and macrophages, we demonstrated that macrophages were required for efficient osteoblast mineralization in response to the physiological remodeling stimulus, elevated extracellular calcium. Notably, OsteoMacs were closely associated with areas of bone modeling in situ, forming a distinctive canopy structure covering >75\% of mature osteoblasts on diaphyseal endosteal surfaces in young growing mice. Depletion of OsteoMacs in vivo using the macrophage-Fas-induced apoptosis (MAFIA) mouse caused complete loss of osteoblast bone-forming surface at this modeling site. Overall, we have demonstrated that OsteoMacs are an integral component of bone tissues and play a novel role in bone homeostasis through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics.}, author = {Chang, Ming K. and Raggatt, Liza-Jane and Alexander, Kylie A. and Kuliwaba, Julia S. and Fazzalari, Nicola L. and Schroder, Kate and Maylin, Erin R. and Ripoll, Vera M. and Hume, David A. and Pettit, Allison R. }, citeulike-article-id = {2973294}, comment = {** field of osteoimmunology - regulatory interaction between bone and immune cells, roles for macrophages in bone biology.... macrophages are intercalated throughout osteal tissues and that they are co-isolated in primary osteoblast preparations. this distinct population of resident tissue macrophages are named OsteoMacs. removing OsteoMacs from primary osteoblast cultures compromised osteoblast function in vitro. macrophages are required for efficient osteoblast differentiation in response to a range of anabolic stimuli in vitro, and that this action is mediated by a soluble factor that is not BMP-2 or -4. Macrophages form a canopy structure covering osteoblasts at sites of bone formation and are present at sites of bone remodelling but are not TRAP positive osteoclast precursors. (1.) M.K. Chang, L.J. Raggatt, J.S. Kuliwaba, N.L. Fazzalari, K.A. Alexander, K. Schroder, E.R. Maylin, V.M. Ripoll, D.A. Hume, A.R. Pettit. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. Manuscript accepted in Journal of Immunology. May 2008 (2.) V.M. Ripoll, N.A. Meadows, L.J. Raggatt, M.K. Chang, A.R. Pettit, A.I. Cassady, D.A. Hume. Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB. Gene. 413 (1-2); 32-41. 2008 (3.) Invited review: A.R. Pettit, M.K. Chang, D.A. Hume, L.J. Raggatt. Osteomacrophage: a new twist on coupling during bone dynamics. Manuscript in Preparation. [** paraphrased from: http://www.cnio.es/eventos/seminarios/docs/13620081643373317.pdf ; 07.08.2008]}, journal = {J Immunol}, keywords = {osteomacs}, month = {July}, number = {2}, pages = {1232--1244}, posted-at = {2008-07-08 20:55:33}, priority = {2}, title = {Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo}, url = {http://www.jimmunol.org/cgi/content/abstract/181/2/1232}, volume = {181}, year = {2008} }

TY - JOUR ID - citeulike:2973294 L3 - citeulike-article-id:2973294 TI - Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo JF - J Immunol VL - 181 IS - 2 SP - 1232 EP - 1244 N2 - Resident macrophages are an integral component of many tissues and are important in homeostasis and repair. This study examines the contribution of resident tissue macrophages to bone physiology. Using immunohistochemistry, we showed that a discrete population of resident macrophages, OsteoMacs, was intercalated throughout murine and human osteal tissues. OsteoMacs were distributed among other bone lining cells within both endosteum and periosteum. Furthermore, OsteoMacs were coisolated with osteoblasts in murine bone explant and calvarial preparations. OsteoMacs made up 15.9% of calvarial preparations and persisted throughout standard osteoblast differentiation cultures. Contrary to previous studies, we showed that it was OsteoMacs and not osteoblasts within these preparations that responded to pathophysiological concentrations of LPS by secreting TNF. Removal of OsteoMacs from calvarial cultures significantly decreased osteocalcin mRNA induction and osteoblast mineralization in vitro. In a Transwell coculture system of enriched osteoblasts and macrophages, we demonstrated that macrophages were required for efficient osteoblast mineralization in response to the physiological remodeling stimulus, elevated extracellular calcium. Notably, OsteoMacs were closely associated with areas of bone modeling in situ, forming a distinctive canopy structure covering >75% of mature osteoblasts on diaphyseal endosteal surfaces in young growing mice. Depletion of OsteoMacs in vivo using the macrophage-Fas-induced apoptosis (MAFIA) mouse caused complete loss of osteoblast bone-forming surface at this modeling site. Overall, we have demonstrated that OsteoMacs are an integral component of bone tissues and play a novel role in bone homeostasis through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics. KW - osteomacs N1 - ** field of osteoimmunology - regulatory interaction between bone and immune cells, roles for macrophages in bone biology.... macrophages are intercalated throughout osteal tissues and that they are co-isolated in primary osteoblast preparations. this distinct population of resident tissue macrophages are named OsteoMacs. removing OsteoMacs from primary osteoblast cultures compromised osteoblast function in vitro. macrophages are required for efficient osteoblast differentiation in response to a range of anabolic stimuli in vitro, and that this action is mediated by a soluble factor that is not BMP-2 or -4. Macrophages form a canopy structure covering osteoblasts at sites of bone formation and are present at sites of bone remodelling but are not TRAP positive osteoclast precursors. (1.) M.K. Chang, L.J. Raggatt, J.S. Kuliwaba, N.L. Fazzalari, K.A. Alexander, K. Schroder, E.R. Maylin, V.M. Ripoll, D.A. Hume, A.R. Pettit. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. Manuscript accepted in Journal of Immunology. May 2008 (2.) V.M. Ripoll, N.A. Meadows, L.J. Raggatt, M.K. Chang, A.R. Pettit, A.I. Cassady, D.A. Hume. Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB. Gene. 413 (1-2); 32-41. 2008 (3.) Invited review: A.R. Pettit, M.K. Chang, D.A. Hume, L.J. Raggatt. Osteomacrophage: a new twist on coupling during bone dynamics. Manuscript in Preparation. [** paraphrased from: http://www.cnio.es/eventos/seminarios/docs/13620081643373317.pdf ; 07.08.2008] AU - Chang, Ming AU - Raggatt, Liza-Jane AU - Alexander, Kylie AU - Kuliwaba, Julia AU - Fazzalari, Nicola AU - Schroder, Kate AU - Maylin, Erin AU - Ripoll, Vera AU - Hume, David AU - Pettit, Allison PY - 2008/07/15/ UR - http://www.jimmunol.org/cgi/content/abstract/181/2/1232 ER -