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Erschienen in: Current Osteoporosis Reports 6/2019

13.11.2019 | Osteoimmunology (M Nakamura and J Lorenzo, Section Editors)

Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification

verfasst von: Koji Matsuo, Robert Dalton Chavez, Emilie Barruet, Edward C. Hsiao

Erschienen in: Current Osteoporosis Reports | Ausgabe 6/2019

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Abstract

Purpose of review

Heterotopic ossification (HO) is associated with inflammation. The goal of this review is to examine recent findings on the roles of inflammation and the immune system in HO. We examine how inflammation changes in fibrodysplasia ossificans progressiva, in traumatic HO, and in other clinical conditions of HO. We also discuss how inflammation may be a target for treating HO.

Recent findings

Both genetic and acquired forms of HO show similarities in their inflammatory cell types and signaling pathways. These include macrophages, mast cells, and adaptive immune cells, along with hypoxia signaling pathways, mesenchymal stem cell differentiation signaling pathways, vascular signaling pathways, and inflammatory cytokines.

Summary

Because there are common inflammatory mediators across various types of HO, these mediators may serve as common targets for blocking HO. Future research may focus on identifying new inflammatory targets and testing combinatorial therapies based on these results.
Literatur
13.
Zurück zum Zitat Hurvitz EA, Mandac BR, Davidoff G, Johnson JH, Nelson VS. Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury. Arch Phys Med Rehabil. 1992;73(5):459–62.PubMed Hurvitz EA, Mandac BR, Davidoff G, Johnson JH, Nelson VS. Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury. Arch Phys Med Rehabil. 1992;73(5):459–62.PubMed
19.
Zurück zum Zitat • Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL, Chan TV, et al. NF-kappaB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018;3(22). https://doi.org/10.1172/jci.insight.122958Analysis of FOP patient-derived sera and monocytes strongly indicates the contribution of myeloid cells in ACVR1-mediated inflammation. • Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL, Chan TV, et al. NF-kappaB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018;3(22). https://​doi.​org/​10.​1172/​jci.​insight.​122958Analysis of FOP patient-derived sera and monocytes strongly indicates the contribution of myeloid cells in ACVR1-mediated inflammation.
20.
Zurück zum Zitat The International Clinical Consortium on FOP The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 2011:4:1-100. The International Clinical Consortium on FOP The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 2011:4:1-100.
24.
Zurück zum Zitat • Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, et al. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015;7(303):303ra137. https://doi.org/10.1126/scitranslmed.aac4358Activin A, a cytokine produced by many cell types including immune cells, appears to be a key driver of heterotopic ossification in FOP. CrossRefPubMedPubMedCentral • Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, et al. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015;7(303):303ra137. https://​doi.​org/​10.​1126/​scitranslmed.​aac4358Activin A, a cytokine produced by many cell types including immune cells, appears to be a key driver of heterotopic ossification in FOP. CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Champagne CM, Takebe J, Offenbacher S, Cooper LF. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone. 2002;30(1):26–31.CrossRefPubMed Champagne CM, Takebe J, Offenbacher S, Cooper LF. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone. 2002;30(1):26–31.CrossRefPubMed
33.
34.
Zurück zum Zitat Gannon FH, Valentine BA, Shore EM, Zasloff MA, Kaplan FS. Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 1998;346:19–25.CrossRef Gannon FH, Valentine BA, Shore EM, Zasloff MA, Kaplan FS. Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 1998;346:19–25.CrossRef
40.
Zurück zum Zitat Convente MR, Chakkalakal SA, Yang E, Caron RJ, Zhang D, Kambayashi T, et al. Depletion of mast cells and macrophages impairs heterotopic ossification in an Acvr1(R206H) mouse model of fibrodysplasia ossificans progressiva. J Bone Miner Res. 2018;33(2):269–82. https://doi.org/10.1002/jbmr.3304.CrossRefPubMed Convente MR, Chakkalakal SA, Yang E, Caron RJ, Zhang D, Kambayashi T, et al. Depletion of mast cells and macrophages impairs heterotopic ossification in an Acvr1(R206H) mouse model of fibrodysplasia ossificans progressiva. J Bone Miner Res. 2018;33(2):269–82. https://​doi.​org/​10.​1002/​jbmr.​3304.CrossRefPubMed
57.
Zurück zum Zitat Jeziorska M, McCollum C, Wooley DE. Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries. Virchows Arch. 1998;433(6):559–65.CrossRefPubMed Jeziorska M, McCollum C, Wooley DE. Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries. Virchows Arch. 1998;433(6):559–65.CrossRefPubMed
59.
Zurück zum Zitat Masi AT, Rodnan GP, Medsger TA, Altman RD, D'Angelo WA, Fries JF, et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–90.CrossRef Masi AT, Rodnan GP, Medsger TA, Altman RD, D'Angelo WA, Fries JF, et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–90.CrossRef
61.
Zurück zum Zitat Hunt JL, Fairman R, Mitchell ME, Carpenter JP, Golden M, Khalapyan T, et al. Bone formation in carotid plaques: a clinicopathological study. Stroke. 2002;33(5):1214–9.CrossRefPubMed Hunt JL, Fairman R, Mitchell ME, Carpenter JP, Golden M, Khalapyan T, et al. Bone formation in carotid plaques: a clinicopathological study. Stroke. 2002;33(5):1214–9.CrossRefPubMed
64.
Zurück zum Zitat Campbell GR, Campbell JH. Vascular smooth muscle and arterial calcification. Z Kardiol. 2000;89(Suppl 2):54–62.CrossRefPubMed Campbell GR, Campbell JH. Vascular smooth muscle and arterial calcification. Z Kardiol. 2000;89(Suppl 2):54–62.CrossRefPubMed
73.
Zurück zum Zitat • Chakkalakal SA, Uchibe K, Convente MR, Zhang D, Economides AN, Kaplan FS, et al. Palovarotene inhibits heterotopic ossification and maintains limb mobility and growth in mice with the human ACVR1(R206H) fibrodysplasia ossificans progressiva (FOP) mutation. J Bone Miner Res. 2016;31(9):1666–75. https://doi.org/10.1002/jbmr.2820Palovalone is a potential therapeutic agent which is currently being tested in clinical trials in FOP patients. It may function by both blocking chondrocyte mineralization as well as immune cell function. CrossRefPubMed • Chakkalakal SA, Uchibe K, Convente MR, Zhang D, Economides AN, Kaplan FS, et al. Palovarotene inhibits heterotopic ossification and maintains limb mobility and growth in mice with the human ACVR1(R206H) fibrodysplasia ossificans progressiva (FOP) mutation. J Bone Miner Res. 2016;31(9):1666–75. https://​doi.​org/​10.​1002/​jbmr.​2820Palovalone is a potential therapeutic agent which is currently being tested in clinical trials in FOP patients. It may function by both blocking chondrocyte mineralization as well as immune cell function. CrossRefPubMed
74.
Zurück zum Zitat Lees-Shepard JB, Nicholas SE, Stoessel SJ, Devarakonda PM, Schneider MJ, Yamamoto M, et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. eLife. 2018;7. https://doi.org/10.7554/eLife.40814. Lees-Shepard JB, Nicholas SE, Stoessel SJ, Devarakonda PM, Schneider MJ, Yamamoto M, et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. eLife. 2018;7. https://​doi.​org/​10.​7554/​eLife.​40814.
Metadaten
Titel
Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification
verfasst von
Koji Matsuo
Robert Dalton Chavez
Emilie Barruet
Edward C. Hsiao
Publikationsdatum
13.11.2019
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 6/2019
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-019-00541-x

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