Osteal macrophages support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model.


Journal

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640

Informations de publication

Date de publication:
11 2021
Historique:
revised: 29 06 2021
received: 18 02 2021
accepted: 14 07 2021
pubmed: 20 7 2021
medline: 15 12 2021
entrez: 19 7 2021
Statut: ppublish

Résumé

Osteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. Although mouse ovariectomy (OVX) models have been repeatedly used, variation in strain, experimental design and assessment modalities have contributed to no single model being confirmed as comprehensively replicating the full gamut of osteoporosis pathological manifestations. We validated an OVX model in adult C3H/HeJ mice and demonstrated that it presents with human postmenopausal osteoporosis features with reduced bone volume in axial and appendicular bone and bone loss in both trabecular and cortical bone including increased cortical porosity. Bone loss was associated with increased osteoclasts on trabecular and endocortical bone and decreased osteoblasts on trabecular bone. Importantly, this OVX model was characterized by delayed fracture healing. Using this validated model, we demonstrated that osteomacs are increased post-OVX on both trabecular and endocortical bone. Dual F4/80 (pan-macrophage marker) and tartrate-resistant acid phosphatase (TRAP) staining revealed osteomacs frequently located near TRAP

Identifiants

pubmed: 34278602
doi: 10.1002/jbmr.4413
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2214-2228

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021 American Society for Bone and Mineral Research (ASBMR).

Références

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795.
Khosla S, Shane E. A crisis in the treatment of osteoporosis. J Bone Miner Res. 2016;31(8):1485-1487.
Lewiecki EM, Leader D, Weiss R, Williams SA. Challenges in osteoporosis awareness and management: results from a survey of US postmenopausal women. J Drug Assess. 2019;8(1):25-31.
Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996;11(3):337-349.
Kushida K, Takahashi M, Kawana K, Inoue T. Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. J Clin Endocrinol Metab. 1995;80(8):2447-2450.
Liu Z, Chen R, Jiang Y, et al. A meta-analysis of serum osteocalcin level in postmenopausal osteoporotic women compared to controls. BMC Musculoskelet Disord. 2019;20:532.
Riggs BL, Melton LJ III, Robb RA, et al. Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res. 2004;19(12):1945-1954.
Riggs BL, Melton LJ III, Robb RA, et al. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res. 2008;23(2):205-214.
Bjornerem AWang X, Bui M, et al. Menopause-related appendicular bone loss is mainly cortical and results in increased cortical porosity. J Bone Miner Res. 2018;33(4):598-605.
Turner RT, Maran A, Lotinun S, et al. Animal models for osteoporosis. Rev Endocr Metab Disord. 2001;2(1):117-127.
Lambers FM, Kuhn G, Schulte FA, Koch K, Müller R. Longitudinal assessment of in vivo bone dynamics in a mouse tail model of postmenopausal osteoporosis. Calcif Tissue Int. 2012;90(2):108-119.
Iwaniec UT, Yuan D, Power RA, Wronski TJ. Strain-dependent variations in the response of cancellous bone to ovariectomy in mice. J Bone Miner Res. 2006;21(7):1068-1074.
Klinck J, Boyd SK. The magnitude and rate of bone loss in ovariectomized mice differs among inbred strains as determined by longitudinal in vivo micro-computed tomography. Calcif Tissue Int. 2008;83(1):70-79.
Li CY, Schaffler MB, Wolde-Semait HT, Hernandez CJ, Jepsen KJ. Genetic background influences cortical bone response to ovariectomy. J Bone Miner Res. 2005;20(12):2150-2158.
Lu Y, Liu Y, Wu C, Li J. Investigating the longitudinal effect of ovariectomy on bone properties using a novel spatiotemporal approach. Ann Biomed Eng. 2018;46(5):749-761.
Roberts BC, Giorgi M, Oliviero S, Wang N, Boudiffa M, Dall'Ara E. The longitudinal effects of ovariectomy on the morphometric, densitometric and mechanical properties in the murine tibia: a comparison between two mouse strains. Bone. 2019;127:260-270.
Bouxsein ML, Myers KS, Shultz KL, Donahue LR, Rosen CJ, Beamer WG. Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Miner Res. 2005;20(7):1085-1092.
Ferguson VL, Ayers RA, Bateman TA, Simske SJ. Bone development and age-related bone loss in male C57BL/6J mice. Bone. 2003;33(3):387-398.
Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. 2007;22(8):1197-1207.
Iwaniec UT, Turner RT. Animal models for osteoporosis. In Marcus R, Feldman D, Dempster DW, Luckey M, Cauley JA, eds. Osteoporosis. 4th ed. San Diego, CA: Academic Press; 2013 pp 939-961.
Cenci S, Toraldo G, Weitzmann MN, et al. Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator. Proc Natl Acad Sci U S A. 2003;100(18):10405-10410.
Cenci S, Weitzmann MN, Gentile MA, Aisa MC, Pacifici R. M-CSF neutralization and egr-1 deficiency prevent ovariectomy-induced bone loss. J Clin Invest. 2000;105(9):1279-1287.
Dou C, Ding N, Zhao C, et al. Estrogen deficiency-mediated M2 macrophage osteoclastogenesis contributes to M1/M2 ratio alteration in ovariectomized osteoporotic mice. J Bone Miner Res. 2018;33(5):899-908.
Muñoz-Garach A, García-Fontana B, Muñoz-Torres M. Nutrients and dietary patterns related to osteoporosis. Nutrients. 2020;12(7):1986.
Alexander KA, Chang MK, Maylin ER, et al. Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res. 2011;26(7):1517-1532.
Batoon L, Millard SM, Wullschleger ME, et al. CD169(+) macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair. Biomaterials. 2019;196:51-66.
Chang MK, Raggatt LJ, Alexander KA, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. 2008;181(2):1232-1244.
Cho SW, Soki FN, Koh AJ, et al. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A. 2014;111(4):1545-1550.
Guihard P, Boutet MA, Brounais-Le Royer B, et al. Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury. Am J Pathol. 2015;185(3):765-775.
Michalski MN, Koh AJ, Weidner S, Roca H, McCauley LK. Modulation of osteoblastic cell efferocytosis by bone marrow macrophages. J Cell Biochem. 2016;117(12):2697-2706.
Raggatt LJ, Wullschleger ME, Alexander KA, et al. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification. Am J Pathol. 2014;184(12):3192-3204.
Vi L, Baht GS, Whetstone H, et al. Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis. J Bone Miner Res. 2014;30(6):1090-1102.
Winkler IG, Sims NA, Pettit AR, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010;116(23):4815-4828.
Papageorgiou M, Föger-Samwald U, Wahl K, Kerschan-Schindl K, Pietschmann P. Age- and strain-related differences in bone microstructure and body composition during development in inbred male mouse strains. Calcif Tissue Int. 2020;106(4):431-443.
Gómez-Barrena E, Rosset P, Lozano D, Stanovici J, Ermthaller C, Gerbhard F. Bone fracture healing: cell therapy in delayed unions and nonunions. Bone. 2015;70:93-101.
Cortet B. Bone repair in osteoporotic bone: postmenopausal and cortisone-induced osteoporosis. Osteoporos Int. 2011;22(6):2007-2010.
Nikolaou VS, Efstathopoulos N, Kontakis G, Kanakaris NK, Giannoudis PV. The influence of osteoporosis in femoral fracture healing time. Injury. 2009;40(6):663-668.
Pang J, Ye M, Gu X, et al. Ovariectomy-induced osteopenia influences the middle and late periods of bone healing in a mouse femoral osteotomy model. Rejuvenation Res. 2015;18(4):356-365.
Miyake Y, Asano K, Kaise H, Uemura M, Nakayama M, Tanaka M. Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. J Clin Invest. 2007;117(8):2268-2278.
Keshvari S, Caruso M, Teakle N, et al. CSF1R-dependent macrophages control postnatal somatic growth and organ maturation. PLoS Genet. 2021;17(6):e1009605.
Filgueira L. Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in osteoclasts combined with other fluorescent dyes and protocols. J Histochem Cytochem. 2004;52(3):411-414.
Wu CA, Pettit AR, Toulson S, Grondahl L, Mackie EJ, Cassady AI. Responses in vivo to purified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) implanted in a murine tibial defect model. J Biomed Mater Res. 2009;91(3):845-854.
Hemmatian H, Laurent MR, Ghazanfari S, et al. Accuracy and reproducibility of mouse cortical bone microporosity as quantified by desktop microcomputed tomography. PLoS One. 2017;12(8):e0182996.
Palacio-Mancheno PE, Larriera AI, Doty SB, Cardoso L, Fritton SP. 3D assessment of cortical bone porosity and tissue mineral density using high-resolution μCT: effects of resolution and threshold method. J Bone Miner Res. 2014;29(1):142-150.
Beekman KM, Zwaagstra M, Veldhuis-Vlug AG, et al. Ovariectomy increases RANKL protein expression in bone marrow adipocytes of C3H/HeJ mice. Am J Physiol Endocrinol Metab. 2019;317(6):e1050-e1054.
Beekman KM, Veldhuis-Vlug AG, den Heijer M, et al. The effect of raloxifene on bone marrow adipose tissue and bone turnover in postmenopausal women with osteoporosis. Bone. 2019;118:62-68.
Yang Y, Luo X, Yan F, et al. Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy. Skeletal Radiol. 2015;44(10):1499-1505.
Mulholland BS, Forwood MR, Morrison NA. Monocyte chemoattractant protein-1 (MCP-1/CCL2) drives activation of bone remodelling and skeletal metastasis. Curr Osteoporos Rep. 2019;17(6):538-547.
Yang XW, Wang XS, Cheng FB, et al. Elevated CCL2/MCP-1 levels are related to disease severity in postmenopausal osteoporotic patients. Clin Lab. 2016;62(11):2173-2181.
Ng PY, Brigitte Patricia Ribet A, Pavlos NJ. Membrane trafficking in osteoclasts and implications for osteoporosis. Biochem Soc Trans. 2019;47(2):639-650.
Armas LA, Recker RR. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am. 2012;41(3):475-486.
Bala Y, Zebaze R, Ghasem-Zadeh A, et al. Cortical porosity identifies women with osteopenia at increased risk for forearm fractures. J Bone Miner Res. 2014;29(6):1356-1362.
Cooper DM, Kawalilak CE, Harrison K, Johnston BD, Johnston JD. Cortical bone porosity: what is it, why is it important, and how can we detect it? Curr Osteoporos Rep. 2016;14(5):187-198.
Piemontese M, Almeida M, Robling AG, et al. Old age causes de novo intracortical bone remodeling and porosity in mice. JCI Insight. 2017;2(17):e93771.
Solberg LB, Brorson SH, Stordalen GA, Baekkevold ES, Andersson G, Reinholt FP. Increased tartrate-resistant acid phosphatase expression in osteoblasts and osteocytes in experimental osteoporosis in rats. Calcif Tissue Int. 2014;94(5):510-521.
Qing H, Ardeshirpour L, Pajevic PD, et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res. 2012;27(5):1018-1029.
Chen L, Yang L, Yao M, et al. Biomechanical characteristics of osteoporotic fracture healing in ovariectomized rats: a systematic review. PLoS One. 2016;11(4):e0153120.
Cheung WH, Miclau T, Chow SK-H, Yang FF, Alt V. Fracture healing in osteoporotic bone. Injury. 2016;47:S21-S26.
Namkung-Matthai H, Appleyard R, Jansen J, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone. 2001;28(1):80-86.
Beil FT, Barvencik F, Gebauer M, et al. Effects of estrogen on fracture healing in mice. J Trauma. 2010;69(5):1259-1265.
Spiro AS, Khadem S, Jeschke A, et al. The SERM raloxifene improves diaphyseal fracture healing in mice. J Bone Miner Metab. 2013;31(6):629-636.
Ding WG, Zhang ZM, Zhang YH, Jiang SD, Jiang LS, Dai LY. Changes of substance P during fracture healing in ovariectomized mice. Regul Pept. 2010;159(1-3):28-34.
Oliver RA, Yu Y, Yee G, Low AK, Diwan AD, Walsh WR. Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats. Osteoporos Int. 2013;24(10):2581-2589.
Haffner-Luntzer M, Kemmler J, Heidler V, et al. Inhibition of midkine augments osteoporotic fracture healing. PLoS One. 2016;11(7):e0159278.
Pepe G, Locati M, Della Torre S, et al. The estrogen-macrophage interplay in the homeostasis of the female reproductive tract. Hum Reprod Update. 2018;24(6):652-672.
Pereira M, Petretto E, Gordon S, Bassett JHD, Williams GR, Behmoaras J. Common signalling pathways in macrophage and osteoclast multinucleation. J Cell Sci. 2018;131(11):jcs216267.
Mohamad SF, Gunawan A, Blosser R, et al. Neonatal osteomacs and bone marrow macrophages differ in phenotypic marker expression and function. J Bone Miner Res. 2021. https://doi.org/10.1002/jbmr.4314.
Mizoguchi T, Muto A, Udagawa N, et al. Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. J Cell Biol. 2009;184(4):541-554.
Muto A, Mizoguchi T, Udagawa N, et al. Lineage-committed osteoclast precursors circulate in blood and settle down into bone. J Bone Miner Res. 2011;26(12):2978-2990.
Batoon L, Millard SM, Raggatt LJ, Pettit AR. Osteomacs and bone regeneration. Curr Osteoporos Rep. 2017;15(4):385-395.
Wu AC, Raggatt LJ, Alexander KA, Pettit AR. Unraveling macrophage contributions to bone repair. Bonekey Rep. 2013;26(2):373.
Reinholt FP, Widholm SM, Ek-Rylander B, Andersson G. Ultrastructural localization of a tartrate-resistant acid ATPase in bone. J Bone Miner Res. 1990;5(10):1055-1061.
Summers KM, Bush SJ, Hume DA. Network analysis of transcriptomic diversity amongst resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system. PLoS Biol. 2020;18(10):e3000859.
Kim H-Y, Alarcon C, Pourteymour S, Wergedal JE, Mohan S. Disruption of claudin-18 diminishes ovariectomy-induced bone loss in mice. Am J Physiol Endocrinol Metab. 2013;304(5):e531-e537.
Hwang Y-H, Kang K-Y, Lee S-J, Nam S-J, Son Y-J, Yee S-T. The protective effects of alisol a 24-acetate from Alisma canaliculatum on ovariectomy induced bone loss in vivo. Molecules. 2016;21(1):74.
Raehtz S, Bierhalter H, Schoenherr D, Parameswaran N, McCabe LR. Estrogen deficiency exacerbates type 1 diabetes-induced bone TNF-α expression and osteoporosis in female mice. Endocrinology. 2017;158(7):2086-2101.

Auteurs

Lena Batoon (L)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Susan M Millard (SM)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Liza J Raggatt (LJ)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Andy C Wu (AC)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Simranpreet Kaur (S)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Lucas W H Sun (LWH)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Kyle Williams (K)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Cheyenne Sandrock (C)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Pei Ying Ng (PY)

Bone Biology and Disease Laboratory, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.

Katharine M Irvine (KM)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Michal Bartnikowski (M)

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

Vaida Glatt (V)

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
Orthopaedic Surgery Department, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.

Nathan J Pavlos (NJ)

Bone Biology and Disease Laboratory, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.

Allison R Pettit (AR)

Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH