Abstract
There is a complex interplay between the cells of the immune system and bone. Immune cells, such as T and NK cells, are able to enhance osteoclast formation via the production of RANKL. Yet there is increasing evidence to show that during the resolution of inflammation or as a consequence of increased osteoclastogenesis there is an anabolic response via the formation of more osteoblasts. Furthermore, osteoblasts themselves are involved in the control of immune cell function, thus promoting the resolution of inflammation. Hence, the concept of “coupling”—how bone formation is linked to resorption—needs to be more inclusive rather than restricting our focus to osteoblast–osteoclast interactions as in a whole organism these cells are never in isolation. This review will investigate the role of immune cells in normal bone homeostasis and in inflammatory diseases where the balance between resorption and formation is lost.
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References
Howard GA et al (1981) Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism. Proc Natl Acad Sci USA 78(5):3204–3208
Martin TJ, Sims NA (2005) Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med 11(2):76–81
Tamma R, Zallone A (2012) Osteoblast and osteoclast crosstalks: from OAF to Ephrin. Inflamm Allergy Drug Targets 11(3):196–200
Takayanagi H (2012) New developments in osteoimmunology. Nat Rev Rheumatol 8(11):684–689
Horton MA et al (1985) On the origin of the osteoclast: the cell surface phenotype of rodent osteoclasts. Calcif Tissue Int 37(1):46–50
Quinn JM et al (2000) Fibroblastic stromal cells express receptor activator of NF-kappaB ligand and support osteoclast differentiation. J Bone Miner Res 15(8):1459–1466
Soderstrom K et al (2010) Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis. Proc Natl Acad Sci USA 107(29):13028–13033
Horwood NJ et al (1999) Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 265(1):144–150
Kong YY et al (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402(6759):304–309
Shinoda K et al (2003) Resting T cells negatively regulate osteoclast generation from peripheral blood monocytes. Bone 33(4):711–720
Rifas L, Arackal S, Weitzmann MN (2003) Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts. J Cell Biochem 88(4):650–659
Gough AK et al (1994) Generalised bone loss in patients with early rheumatoid arthritis. Lancet 344(8914):23–27
Loftus EV Jr et al (2003) Risk of fracture in ulcerative colitis: a population-based study from Olmsted County, Minnesota. Clin Gastroenterol Hepatol 1(6):465–473
Magrey M, Khan MA (2010) Osteoporosis in ankylosing spondylitis. Curr Rheumatol Rep 12(5):332–336
Spector TD et al (1993) Risk of vertebral fracture in women with rheumatoid arthritis. BMJ 306(6877):558
Eyerich S et al (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119(12):3573–3585
Murphy CA et al (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198(12):1951–1957
Takayanagi H et al (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408(6812):600–605
Sato K, Takayanagi H (2006) Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 18(4):419–426
Takayanagi H (2005) Inflammatory bone destruction and osteoimmunology. J Periodontal Res 40(4):287–293
Kotake S et al (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103(9):1345–1352
Zaiss MM et al (2010) Regulatory T cells protect from local and systemic bone destruction in arthritis. J Immunol 184(12):7238–7246
Kim YG et al (2007) Human CD4+CD25+ regulatory T cells inhibit the differentiation of osteoclasts from peripheral blood mononuclear cells. Biochem Biophys Res Commun 357(4):1046–1052
Wythe SE et al (2013) Targeted delivery of cytokine therapy to rheumatoid tissue by a synovial targeting peptide. Ann Rheum Dis 72(1):129–135
Appel H et al (2006) Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum 54(9):2845–2851
Bowness P et al (2011) Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol 186(4):2672–2680
Daoussis D et al (2010) Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62(1):150–158
Appel H et al (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60(11):3257–3262
Chen HA et al (2010) Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol 37(10):2126–2132
Vosse D et al (2008) Association of markers of bone- and cartilage-degradation with radiological changes at baseline and after 2 years follow-up in patients with ankylosing spondylitis. Rheumatology (Oxford) 47(8):1219–1222
Braun J, Baraliakos X (2011) Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann Rheum Dis 70(Suppl 1):i97–i103
Byrne FR et al (2005) CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin. Gut 54(1):78–86
Ruutu M et al (2012) Beta-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis Rheum 64(7):2211–2222
Pacifici R (2007) T cells and postmenopausal osteoporosis in murine models. Arthritis Res Ther 9(2):102
Zaidi M (2007) Skeletal remodeling in health and disease. Nat Med 13(7):791–801
Jilka RL et al (1998) Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow. Evidence for autonomy from factors released during bone resorption. J Clin Invest 101(9):1942–1950
Kimble RB et al (1996) Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1 and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production. J Biol Chem 271(46):28890–28897
Cenci S et al (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106(10):1229–1237
Lee SK et al (2006) T lymphocyte-deficient mice lose trabecular bone mass with ovariectomy. J Bone Miner Res 21(11):1704–1712
Yamaza T et al (2008) Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One 3(7):e2615
Roggia C et al (2001) Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci USA 98(24):13960–13965
Li JY et al (2011) Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand. Proc Natl Acad Sci USA 108(2):768–773
Grassi F et al (2007) Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. Proc Natl Acad Sci USA 104(38):15087–15092
Li Y et al (2007) B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood 109(9):3839–3848
DeSelm CJ et al (2012) IL-17 mediates estrogen-deficient osteoporosis in an Act1-dependent manner. J Cell Biochem 113(9):2895–2902
Fox SW, Chambers TJ (2000) Interferon-gamma directly inhibits TRANCE-induced osteoclastogenesis. Biochem Biophys Res Commun 276(3):868–872
Kotake S et al (2005) IFN-gamma-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL. Eur J Immunol 35(11):3353–3363
Madyastha PR et al (2000) IFN-gamma enhances osteoclast generation in cultures of peripheral blood from osteopetrotic patients and normalizes superoxide production. J Interferon Cytokine Res 20(7):645–652
Sato K et al (1992) Prolonged decrease of serum calcium concentration by murine gamma-interferon in hypercalcemic, human tumor (EC-GI)-bearing nude mice. Cancer Res 52(2):444–449
Tohkin M et al (1994) Comparative study of inhibitory effects by murine interferon gamma and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK). Cancer Immunol Immunother 39(3):155–160
Arnoldi J, Gerdes J, Flad HD (1990) Immunohistologic assessment of cytokine production of infiltrating cells in various forms of leprosy. Am J Pathol 137(4):749–753
Baker PJ et al (1999) CD4+ T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun 67(6):2804–2809
Cenci S et al (2003) Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci USA 100(18):10405–10410
Goodman GR et al (1999) Interferon-alpha, unlike interferon-gamma, does not cause bone loss in the rat. Bone 25(4):459–463
Key LL Jr et al (1995) Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 332(24):1594–1599
Mann GN et al (1994) Interferon-gamma causes loss of bone volume in vivo and fails to ameliorate cyclosporin A-induced osteopenia. Endocrinology 135(3):1077–1083
Rodriguiz RM, Key LL Jr, Ries WL (1993) Combination macrophage-colony stimulating factor and interferon-gamma administration ameliorates the osteopetrotic condition in microphthalmic (mi/mi) mice. Pediatr Res 33(4 Pt 1):384–389
Duque G et al (2011) Interferon-gamma plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice. J Bone Miner Res 26(7):1472–1483
Gao Y et al (2007) IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest 117(1):122–132
Tyagi AM et al (2012) Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS One 7(9):e44552
Goswami J et al (2009) A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss. Eur J Immunol 39(10):2831–2839
Rivollier A et al (2004) Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment. Blood 104(13):4029–4037
Speziani C et al (2007) Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines. Eur J Immunol 37(3):747–757
Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289(5484):1504–1508
Alnaeeli M, Penninger JM, Teng YT (2006) Immune interactions with CD4+ T cells promote the development of functional osteoclasts from murine CD11c+ dendritic cells. J Immunol 177(5):3314–3326
Maitra R et al (2010) Dendritic cell–mediated in vivo bone resorption. J Immunol 185(3):1485–1491
Jacome-Galarza CE et al (2013) Identification, characterization and isolation of a common progenitor for osteoclasts, macrophages and dendritic cells from murine bone marrow and periphery. J Bone Miner Res 28:1203–1213
Mizoguchi T et al (2009) Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. J Cell Biol 184(4):541–554
Charles JF et al (2012) Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest 122(12):4592–4605
Grcevic D et al (2006) Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos. Clin Exp Immunol 146(1):146–158
Gupta N et al (2010) IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage. J Immunol 185(4):2261–2272
Paust S, von Andrian UH (2011) Natural killer cell memory. Nat Immunol 12(6):500–508
Vivier E et al (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331(6013):44–49
Grom AA et al (2003) Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome. J Pediatr 142(3):292–296
Pridgeon C et al (2003) Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright, CD94bright, CD158negative phenotype. Rheumatology (Oxford) 42(7):870–878
Lo CK et al (2008) Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin-17 production. Arthritis Rheum 58(9):2700–2711
Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13(2):101–117
Godfrey DI, Rossjohn J (2011) New ways to turn on NKT cells. J Exp Med 208(6):1121–1125
Hu M et al (2011) Activated invariant NKT cells regulate osteoclast development and function. J Immunol 186(5):2910–2917
Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30:221–241
Blin-Wakkach C et al (2004) Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice. J Bone Miner Res 19(7):1137–1143
Dougall WC et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13(18):2412–2424
Kong YY et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397(6717):315–323
Yun TJ et al (2001) Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function. J Immunol 166(3):1482–1491
Weitzmann MN et al (2000) B lymphocytes inhibit human osteoclastogenesis by secretion of TGFbeta. J Cell Biochem 78(2):318–324
Li Y et al (2007) Ovariectomy-induced bone loss occurs independently of B cells. J Cell Biochem 100(6):1370–1375
Raggatt LJ et al (2013) Absence of B cells does not compromise intramembranous bone formation during healing in a tibial injury model. Am J Pathol 182(5):1501–1508
Nakken B et al (2011) B-cells and their targeting in rheumatoid arthritis—current concepts and future perspectives. Autoimmun Rev 11(1):28–34
Bluml S et al (2013) B-cell targeted therapeutics in clinical development. Arthritis Res Ther 15(Suppl 1):S4
Loutis N, Bruckner P, Pataki A (1988) Induction of erosive arthritis in mice after passive transfer of anti-type II collagen antibodies. Agents Actions 25(3–4):352–359
Taylor PC, Plater-Zyberk C, Maini RN (1995) The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA/1 (H-2q) to SCID (H-2d) mice. Eur J Immunolo 25(3):763–769
Svensson L et al (1998) B cell–deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol 111(3):521–526
Edwards JC, Leandro MJ, Cambridge G (2002) B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune disorders. Biochem Soc Trans 30(4):824–828
Moore J et al (2004) A phase II study of rituximab in rheumatoid arthritis patients with recurrent disease following haematopoietic stem cell transplantation. Bone Marrow Transplant 34(3):241–247
Horwood NJ, Urbaniak AM, Danks L (2012) Tec family kinases in inflammation and disease. Int Rev Immunol 31(2):87–103
Bedi B et al (2012) Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH. Proc Natl Acad Sci USA 109(12):E725–E733
Bar-Shavit Z (2007) The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem 102(5):1130–1139
Nakagawa H et al (1993) Influence of monocyte–macrophage lineage cells on alkaline phosphatase activity of developing osteoblasts derived from rat bone marrow stromal cells. Nippon Seikeigeka Gakkai Zasshi 67(5):480–489
Rifas L et al (1989) Monokines produced by macrophages stimulate the growth of osteoblasts. Connect Tissue Res 23(2–3):163–178
Champagne CM et al (2002) Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone 30(1):26–31
Hume DA, Loutit JF, Gordon S (1984) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of bone and associated connective tissue. J Cell Sci 66:189–194
Chang MK et al (2008) Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 181(2):1232–1244
Alexander KA et al (2011) Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res 26(7):1517–1532
Nicolaidou V et al (2012) Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation. PLoS One 7(7):e39871
Guihard P et al (2012) Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling. Stem Cells 30(4):762–772
Zarling JM et al (1986) Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci USA 83(24):9739–9743
Walker EC et al (2010) Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J Clin Invest 120(2):582–592
Malik N et al (1995) Developmental abnormalities in mice transgenic for bovine oncostatin M. Mol Cell Biol 15(5):2349–2358
de Hooge AS et al (2002) Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in knee joints of mice, despite synovial inflammation and up-regulated expression of interleukin-6 and receptor activator of nuclear factor-kappa B ligand. Am J Pathol 160(5):1733–1743
Levy JB et al (1996) Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells. Endocrinology 137(4):1159–1165
Bellido T et al (1997) Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation. Endocrinology 138(9):3666–3676
Fujio Y et al (2004) Signals through gp130 upregulate Wnt5a and contribute to cell adhesion in cardiac myocytes. FEBS Lett 573(1–3):202–206
Katoh M (2007) STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer. Int J Mol Med 19(2):273–278
Botelho FM, Edwards DR, Richards CD (1998) Oncostatin M stimulates c-Fos to bind a transcriptionally responsive AP-1 element within the tissue inhibitor of metalloproteinase-1 promoter. J Biol Chem 273(9):5211–5218
Jochum W et al (2000) Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nat Med 6(9):980–984
Sabatakos G et al (2000) Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis. Nat Med 6(9):985–990
Sims NA, Walsh NC (2010) GP130 cytokines and bone remodelling in health and disease. BMB Rep 43(8):513–523
Hamilton TA (2002) Molecular basis of macrophage activation: from gene expression to phenotypic diversity. In: Bourke BL (ed) The macrophage, 2nd edn. Oxford University Press, Oxford
Porta C et al (2009) Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci USA 106(35):14978–14983
Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787–795
Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32(5):593–604
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969
Fleetwood AJ et al (2007) Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J Immunol 178(8):5245–5252
Smith W, Feldmann M, Londei M (1998) Human macrophages induced in vitro by macrophage colony-stimulating factor are deficient in IL-12 production. Eur J Immunol 28(8):2498–2507
Tadokoro CE, de Almeida AI (2001) Bone marrow–derived macrophages grown in GM-CSF or M-CSF differ in their ability to produce IL-12 and to induce IFN-gamma production after stimulation with Trypanosoma cruzi antigens. Immunol Lett 77(1):31–38
Verreck FA et al (2006) Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation. J Leukoc Biol 79(2):285–293
Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8(7):533–544
Groh ME et al (2005) Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 33(8):928–934
Francois M et al (2012) Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther 20(1):187–195
Kim J, Hematti P (2009) Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 37(12):1445–1453
Maggini J et al (2010) Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One 5(2):e9252
Nemeth K et al (2009) Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 15(1):42–49
Jones S et al (2007) The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells. J Immunol 179(5):2824–2831
Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822
Kawaguchi H et al (1995) The role of prostaglandins in the regulation of bone metabolism. Clin Orthop Relat Res 313:36–46
Li L et al (2006) Regulation of bone biology by prostaglandin endoperoxide H synthases (PGHS): a rose by any other name. Cytokine Growth Factor Rev 17(3):203–216
Xie C et al (2008) COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing. Bone 43(6):1075–1083
Nagata T et al (1994) Effect of prostaglandin E2 on mineralization of bone nodules formed by fetal rat calvarial cells. Calcif Tissue Int 55(6):451–457
Ninomiya T et al (2011) Prostaglandin E2 receptor EP4-selective agonist (ONO-4819) increases bone formation by modulating mesenchymal cell differentiation. Eur J Pharmacol 650(1):396–402
Weinreb M, Suponitzky I, Keila S (1997) Systemic administration of an anabolic dose of PGE2 in young rats increases the osteogenic capacity of bone marrow. Bone 20(6):521–526
Repovic P, Benveniste EN (2002) Prostaglandin E2 is a novel inducer of oncostatin-M expression in macrophages and microglia. J Neurosci 22(13):5334–5343
Bystrom J et al (2008) Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP. Blood 112(10):4117–4127
Rajakariar R et al (2008) Novel biphasic role for lymphocytes revealed during resolving inflammation. Blood 111(8):4184–4192
Pettit AR et al (2008) Osteal macrophages: a new twist on coupling during bone dynamics. Bone 43(6):976–982
Ren G et al (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2(2):141–150
Chen L et al (2008) Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One 3(4):e1886
Xu W et al (2006) IL-10-producing macrophages preferentially clear early apoptotic cells. Blood 107(12):4930–4937
Kawanaka N et al (2002) CD14+, CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. Arthritis Rheum 46(10):2578–2586
Rossol M et al (2012) The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum 64(3):671–677
Chiappetta N, Gruber B (2006) The role of mast cells in osteoporosis. Semin Arthritis Rheum 36(1):32–36
Seitz S et al (2013) Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int 24:2325–2334
Martin T, Gooi JH, Sims NA (2009) Molecular mechanisms in coupling of bone formation to resorption. Crit Rev Eukaryot Gene Expr 19(1):73–88
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Wythe, S.E., Nicolaidou, V. & Horwood, N.J. Cells of the Immune System Orchestrate Changes in Bone Cell Function. Calcif Tissue Int 94, 98–111 (2014). https://doi.org/10.1007/s00223-013-9764-0
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DOI: https://doi.org/10.1007/s00223-013-9764-0