nach oben

Current Osteoporosis Reports

Erschienen in:

14.04.2021 | Genetics (D Karasik and C Ackert-Bicknell, Section Editors)

Do Interactions of Vitamin D₃ and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva?

verfasst von: Jessica L. Pierce, Daniel S. Perrien

Erschienen in: Current Osteoporosis Reports | Ausgabe 3/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D₃ in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D’s effects in FOP by exploring relevant intersections of VD₃ with mechanisms of FOP flares.

Recent Findings

In vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D₃ protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP.

Summary

There appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.

Bridges AJ, Hsu KC, Singh A, Churchill R, Miles J. Fibrodysplasia (myositis) ossificans progressiva. Semin Arthritis Rheum. 1994;24(3).

Kaplan FS, Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol. 2008;22(1):191–205. https://doi.org/10.1016/j.berh.2007.11.007.CrossRefPubMedPubMedCentral

Dey D, Bagarova J, Hatsell SJ, Armstrong KA, Huang L, Ermann J, et al. Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Sci Transl Med. 2016, 8(366):366ra163. https://doi.org/10.1126/scitranslmed.aaf1090.

Baujat G, Choquet R, Bouee S, Jeanbat V, Courouve L, Ruel A, et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis. 2017;12(1):123. https://doi.org/10.1186/s13023-017-0674-5.CrossRefPubMedPubMedCentral

Mahboubi S, Glaser DL, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva. Pediatr Radiol. 2001;31(5):307–14. https://doi.org/10.1007/s002470100447.CrossRefPubMed

Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev. 2013;10(2):437–48.PubMedPubMedCentral

Zaghloul KA, Heuer GG, Guttenberg MD, Shore EM, Kaplan FS, Storm PB. Lumbar puncture and surgical intervention in a child with undiagnosed fibrodysplasia ossificans progressiva. J Neurosurg Pediatr. 2008;1(1):91–4. https://doi.org/10.3171/PED-08/01/091.CrossRefPubMed

Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006;38(5):525–7. https://doi.org/10.1038/ng1783.CrossRefPubMed

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.aac4358.CrossRefPubMedPubMedCentral

10.

Lees-Shepard JB, Yamamoto M, Biswas AA, Stoessel SJ, Nicholas SE, Cogswell CA, et al. Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva. Nat Commun. 2018;9(1):471. https://doi.org/10.1038/s41467-018-02872-2.CrossRefPubMedPubMedCentral

11.

Wentworth KL, Masharani U, Hsiao EC. Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva. Br J Clin Pharmacol. 2019;85(6):1180–7. https://doi.org/10.1111/bcp.13823.CrossRefPubMedPubMedCentral

12.

Haviv R, Moshe V, De Benedetti F, Prencipe G, Rabinowicz N, Uziel Y. Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome? Pediatr Rheumatol Online J. 2019;17(1):84. https://doi.org/10.1186/s12969-019-0386-6.CrossRefPubMedPubMedCentral

13.

Kaplan FS, Andolina JR, Adamson PC, Teachey DT, Finklestein JZ, Ebb DH, et al. Early clinical observations on the use of imatinib mesylate in FOP: a report of seven cases. Bone. 2018;109:276–80. https://doi.org/10.1016/j.bone.2017.07.019.CrossRefPubMed

14.

Hino K, Zhao C, Horigome K, Nishio M, Okanishi Y, Nagata S, et al. An mTOR signaling modulator suppressed heterotopic ossification of fibrodysplasia ossificans progressiva. Stem Cell Reports. 2018;11(5):1106–19. https://doi.org/10.1016/j.stemcr.2018.10.007.CrossRefPubMedPubMedCentral

15.

Williams E, Bullock AN. Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2. Bone. 2017;109:251–8. https://doi.org/10.1016/j.bone.2017.09.004.CrossRefPubMed

16.

Agarwal S, Loder SJ, Breuler C, Li J, Cholok D, Brownley C, et al. Strategic targeting of multiple BMP receptors prevents trauma-induced heterotopic ossification. Mol Ther. 2017;25(8):1974–87. https://doi.org/10.1016/j.ymthe.2017.01.008.CrossRefPubMedPubMedCentral

17.

Sinha S, Uchibe K, Usami Y, Pacifici M, Iwamoto M. Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent. Bone. 2016;90:59–68. https://doi.org/10.1016/j.bone.2016.02.008.CrossRefPubMedPubMedCentral

18.

Micha D, Voermans E, Eekhoff MEW, van Essen HW, Zandieh-Doulabi B, Netelenbos C, et al. Inhibition of TGFbeta signaling decreases osteogenic differentiation of fibrodysplasia ossificans progressiva fibroblasts in a novel in vitro model of the disease. Bone. 2016;84:169–80. https://doi.org/10.1016/j.bone.2016.01.004.CrossRefPubMed

19.

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 ACVR1R206H fibrodysplasia ossificans progressiva (FOP) mutation. J Bone Miner Res. 2016;31:1666–75. https://doi.org/10.1002/jbmr.2820.CrossRefPubMed

20.

Pignolo RJ, Baujat G, Brown MA, De Cunto C, Di Rocco M, Hsiao EC, et al. Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes. Orphanet Journal of Rare Diseases. 2019;14(1). https://doi.org/10.1186/s13023-019-1068-7.

21.

Pignolo RJ, Bedford-Gay C, Liljesthrom M, Durbin-Johnson BP, Shore EM, Rocke DM, et al. The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment. J Bone Miner Res. 2016;31(3):650–6. https://doi.org/10.1002/jbmr.2728.CrossRefPubMed

22.

Al Kaissi A, Kenis V, Ben Ghachem M, Hofstaetter J, Grill F, Ganger R, et al. The diversity of the clinical phenotypes in patients with fibrodysplasia ossificans progressiva. J Clin Med Res. 2016;8(3):246–53. https://doi.org/10.14740/jocmr2465w.CrossRefPubMedPubMedCentral

23.

Nguyen-Yamamoto L, Tanaka K-I, St–Arnaud R, Goltzman D. Vitamin D–regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification. JCI Insight. 2019;4(13). https://doi.org/10.1172/jci.insight.126467.

24•.

. Wakahashi K, Minagawa K, Kawano Y, Kawano H, Suzuki T, Ishii S, et al. Vitamin D receptor–mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis. Blood. 2019;133(15):1619–29. https://doi.org/10.1182/blood-2018-09-876615Wakahashi et al. showed that vitamin D promotes the proinflammatory polarization of macrophages via the VDR. This could be a key mechanistic link to heterotopic ossification and FOP, as the importance of macrophages has been demonstrated in multiple mouse models of HO and FOP.CrossRefPubMed

25.

Pacifici M, Shore EM. Common mutations in ALK2/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders. Cytokine Growth Factor Rev. 2016;27:93–104. https://doi.org/10.1016/j.cytogfr.2015.12.007.CrossRefPubMed

26.

Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009;30(3):379–90. https://doi.org/10.1002/humu.20868.CrossRefPubMedPubMedCentral

27.

• Hatsell SJ, Idone V, Alessi 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) This study demonstrates that ALK2^R206H is sensitized to inappropriate activation by Activin A, which is required for HO progression in the ACVR1^R206H mouse model of FOP.

28.

Alessi Wolken DM, Idone V, Hatsell SJ, Yu PB, Economides AN. The obligatory role of Activin A in the formation of heterotopic bone in fibrodysplasia ossificans progressiva. Bone. 2018;109:210–7. https://doi.org/10.1016/j.bone.2017.06.011.CrossRefPubMed

29.

Upadhyay J, Xie L, Huang L, Das N, Stewart RC, Lyon MC, et al. The expansion of heterotopic bone in fibrodysplasia ossificans progressiva is activin A-dependent. J Bone Miner Res. 2017;32(12):2489–99. https://doi.org/10.1002/jbmr.3235.CrossRefPubMed

30.

Pignolo RJ, Bedford-Gay C, Liljesthröm M, Durbin-Johnson BP, Shore EM, Rocke DM, et al. The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment. J Bone Miner Res. 2016;31(3):650–6. https://doi.org/10.1002/jbmr.2728.CrossRefPubMed

31.

Pignolo RJ, Kaplan FS. Clinical staging of fibrodysplasia ossificans progressiva (FOP). Bone. 2017;109:111–4. https://doi.org/10.1016/j.bone.2017.09.014.CrossRefPubMed

32.

Shah PB, Zasloff MA, Drummond D, Kaplan FS. Spinal deformity in patients who have fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 1994;76(10):1442–50.CrossRef

33.

Gannon FH, Glaser D, Caron R, Thompson LD, Shore EM, Kaplan FS. Mast cell involvement in fibrodysplasia ossificans progressiva. Hum Pathol. 2001;32(8):842–8. https://doi.org/10.1053/hupa.2001.26464.CrossRefPubMed

34.

Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: clinical and genetic aspects. Orphanet Journal of Rare Diseases. 2011;6(1):80. https://doi.org/10.1186/1750-1172-6-80.CrossRefPubMedPubMedCentral

35.

Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am. 1993;75(2):215–9.CrossRef

36.

Kaplan FS, Tabas JA, Gannon FH, Finkel G, Hahn GV, Zasloff MA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. J Bone Joint Surg Am. 1993;75(2):220–30. https://doi.org/10.2106/00004623-199302000-00009.CrossRefPubMed

37.

• 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.3304This represents the first demonstration that innate immune cells contribute to HO in a model of FOP that expresses the clinically relevant ALK2^R206H mutation.CrossRefPubMed

38.

Merchant R, Sainani NI, Lawande MA, Pungavkar SA, Patkar DP, Walawalkar A. Pre- and post-therapy MR imaging in fibrodysplasia ossificans progressiva. Pediatr Radiol. 2006;36(10):1108–11. https://doi.org/10.1007/s00247-006-0270-7.CrossRefPubMed

39.

Chakkalakal SA, Zhang D, Culbert AL, Convente MR, Caron RJ, Wright AC, et al. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res. 2012;27(8):1746–56. https://doi.org/10.1002/jbmr.1637.CrossRefPubMed

40.

Smith R, Athanasou NA, Vipond SE. Fibrodysplasia (myositis) ossificans progressiva: clinicopathological features and natural history. QJM. 1996;89(6):445–6. https://doi.org/10.1093/qjmed/89.6.445.CrossRefPubMed

41.

Botman E, Raijmakers P, Yaqub M, Teunissen B, Netelenbos C, Lubbers W, et al. Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: an [(18)F]NaF PET/CT study. Bone. 2019;124:1–6. https://doi.org/10.1016/j.bone.2019.03.009.CrossRefPubMed

42.

Eekhoff EMW, Botman E, Coen Netelenbos J, de Graaf P, Bravenboer N, Micha D, et al. [18F]NaF PET/CT scan as an early marker of heterotopic ossification in fibrodysplasia ossificans progressiva. Bone. 2018;109:143–6. https://doi.org/10.1016/j.bone.2017.08.012.CrossRefPubMed

43.

Eekhoff EMW, Netelenbos JC, de Graaf P, Hoebink M, Bravenboer N, Micha D, et al. Flare-up after maxillofacial surgery in a patient with fibrodysplasia ossificans progressiva: an [(18)F]-NaF PET/CT study and a systematic review. JBMR Plus. 2018;2(1):55–8. https://doi.org/10.1002/jbm4.10008.CrossRefPubMed

44.

Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, et al. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008;14(12):1363–9. https://doi.org/10.1038/nm.1888.CrossRefPubMedPubMedCentral

45.

Culbert AL, Chakkalakal SA, Theosmy EG, Brennan TA, Kaplan FS, Shore EM. Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification. Stem Cells. 2014;32(5):1289–300. https://doi.org/10.1002/stem.1633.CrossRefPubMedPubMedCentral

46.

Dey D, Bagarova J, Hatsell SJ, Armstrong KA, Huang L, Ermann J, et al. Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Sci Transl Med. 2016;8(366):366ra163–366ra1. https://doi.org/10.1126/scitranslmed.aaf1090.CrossRefPubMedPubMedCentral

47.

Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44(3):450–62. https://doi.org/10.1016/j.immuni.2016.02.015.CrossRefPubMedPubMedCentral

48.

Kan L, Liu Y, McGuire TL, Berger DM, Awatramani RB, Dymecki SM, et al. Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells. 2009;27(1):150–6. https://doi.org/10.1634/stemcells.2008-0576.CrossRefPubMedPubMedCentral

49.

Kan L, Lounev VY, Pignolo RJ, Duan L, Liu Y, Stock SR, et al. Substance P signaling mediates BMP-dependent heterotopic ossification. J Cell Biochem. 2011;112(10):2759–72. https://doi.org/10.1002/jcb.23259.CrossRefPubMedPubMedCentral

50.

Hino K, Horigome K, Nishio M, Komura S, Nagata S, Zhao C, et al. Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. J Clin Invest. 2017;127(9):3339–52. https://doi.org/10.1172/JCI93521.CrossRefPubMedPubMedCentral

51.

Haviv R, Moshe V, De Benedetti F, Prencipe G, Rabinowicz N, Uziel Y. Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome? Pediatr Rheumatol. 2019;17(1). https://doi.org/10.1186/s12969-019-0386-6.

52.

Bagarova J, Vonner AJ, Armstrong KA, Borgermann J, Lai CSC, Deng DY, et al. Constitutively active ALK2 receptor mutants require type ii receptor cooperation. Mol Cell Biol. 2013;33(12):2413–24. https://doi.org/10.1128/mcb.01595-12.CrossRefPubMedPubMedCentral

53.

Holick MF, Frommer JE, McNeill SC, Richtand NM, Henley JW, Potts JT. Photometabolism of 7-dehydrocholesterol to previtamin D3 in skin. Biochem Biophys Res Commun. 1977;76(1):107–14. https://doi.org/10.1016/0006-291x(77)91674-6.CrossRefPubMed

54.

Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408. https://doi.org/10.1152/physrev.00014.2015.CrossRefPubMed

55.

Bikle DD, Schwartz J. Vitamin D binding protein, total and free vitamin D levels in different physiological and pathophysiological conditions. Front Endocrinol. 2019;10. https://doi.org/10.3389/fendo.2019.00317.

56.

Doroudi M, Boyan BD, Schwartz Z. Rapid 1α,25(OH) 2 D 3 membrane-mediated activation of Ca 2+ /calmodulin-dependent protein kinase II in growth plate chondrocytes requires Pdia3. PLAA and caveolae. 2014;55(sup1):125–8. https://doi.org/10.3109/03008207.2014.923882.CrossRef

57.

Chen J, Doroudi M, Cheung J, Grozier AL, Schwartz Z, Boyan BD. Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1α,25(OH)2D3. Cell Signal. 2013;25(12):2362–73. https://doi.org/10.1016/j.cellsig.2013.07.020.CrossRefPubMed

58.

Pike JW, Christakos S. Biology and mechanisms of action of the vitamin D hormone. Endocrinol Metab Clin N Am. 2017;46(4):815–43. https://doi.org/10.1016/j.ecl.2017.07.001.CrossRef

59.

Jiang X, Huang B, Yang H, Li G, Zhang C, Yang G, et al. TGF-β1 is involved in vitamin D-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating the ERK/JNK pathway. Cell Physiol Biochem. 2017;42(6):2230–41. https://doi.org/10.1159/000479997.CrossRefPubMed

60.

Asmussen N, Lin Z, McClure MJ, Schwartz Z, Boyan BD. Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation. Steroids. 2019;142:43–7. https://doi.org/10.1016/j.steroids.2017.12.003.CrossRefPubMed

61.

Oishi T, Uezumi A, Kanaji A, Yamamoto N, Yamaguchi A, Yamada H, et al. Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells. PLoS One. 2013;8(2):e56641. https://doi.org/10.1371/journal.pone.0056641.CrossRefPubMedPubMedCentral

62.

Uezumi A, Fukada S, Yamamoto N, Ikemoto-Uezumi M, Nakatani M, Morita M, et al. Identification and characterization of PDGFRalpha+ mesenchymal progenitors in human skeletal muscle. Cell Death Dis. 2014;5:e1186. https://doi.org/10.1038/cddis.2014.161.CrossRefPubMedPubMedCentral

63.

Fu B, Wang H, Wang J, Barouhas I, Liu W, Shuboy A, et al. Epigenetic regulation of BMP2 by 1,25-dihydroxyvitamin D3 through DNA methylation and histone modification. PLoS One. 2013;8(4):e61423. https://doi.org/10.1371/journal.pone.0061423

64.

Woeckel VJ, Van Der Eerden BCJ, Schreuders-Koedam M, Eijken M, Van Leeuwen JPTM. 1α,25-dihydroxyvitamin D3stimulates activin A production to fine-tune osteoblast-induced mineralization. J Cell Physiol. 2013;228(11):2167–74. https://doi.org/10.1002/jcp.24388.CrossRefPubMed

65.

Wang T-T, Tavera-Mendoza LE, Laperriere D, Libby E, Burton Macleod N, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005;19(11):2685–95. https://doi.org/10.1210/me.2005-0106.CrossRefPubMed

66.

Chen J, Dosier CR, Park JH, De S, Guldberg RE, Boyan BD, et al. Mineralization of three-dimensional osteoblast cultures is enhanced by the interaction of 1α,25-dihydroxyvitamin D3 and BMP2 via two specific vitamin D receptors. J Tissue Eng Regen Med. 2016;10(1):40–51. https://doi.org/10.1002/term.1770.CrossRefPubMed

67.

Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN. 1,25(OH)2Vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology. 2011;152(8):2976–86. https://doi.org/10.1210/en.2011-0159.CrossRefPubMedPubMedCentral

68.

Braga M, Simmons Z, Norris KC, Ferrini MG, Artaza JN. Vitamin D induces myogenic differentiation in skeletal muscle derived stem cells. Endocrine Connections. 2017;6(3):139–50. https://doi.org/10.1530/ec-17-0008.CrossRefPubMedPubMedCentral

69.

Srikuea R, Zhang X, Park-Sarge OK, Esser KA. VDR and CYP27B1 are expressed in C2C12 cells and regenerating skeletal muscle: potential role in suppression of myoblast proliferation. Am J Phys Cell Phys. 2012;303(4):C396–405. https://doi.org/10.1152/ajpcell.00014.2012.CrossRef

70.

Avcioglu G, Özbek Ipteç B, Akcan G, Görgün B, Fidan K, Carhan A, et al. Effects of 1,25-Dihydroxy vitamin D3 on TNF-α induced inflammation in human chondrocytes and SW1353 cells: a possible role for toll-like receptors. Mol Cell Biochem. 2019;464:131–42. https://doi.org/10.1007/s11010-019-03655-z.CrossRefPubMed

71.

Li W, Liu Z, Tang R, Ouyang S, Li S, Wu J. Vitamin D inhibits palmitate-induced macrophage pro-inflammatory cytokine production by targeting the MAPK pathway. Immunol Lett. 2018;202:23–30. https://doi.org/10.1016/j.imlet.2018.07.009.CrossRefPubMed

72.

Tulk SE, Liao K-C, Muruve DA, Li Y, Beck PL, Macdonald JA. Vitamin D3metabolites enhance the NLRP3-dependent secretion of IL-1β from human THP-1 monocytic cells. J Cell Biochem. 2015;116(5):711–20. https://doi.org/10.1002/jcb.24985.CrossRefPubMed

73.

Kew RR, Tabrizian T, Vosswinkel JA, Davis JE, Jawa RS. Vitamin D–binding protein deficiency in mice decreases systemic and select tissue levels of inflammatory cytokines in a murine model of acute muscle injury. J Trauma Acute Care Surg. 2018;84(6):847–54. https://doi.org/10.1097/ta.0000000000001875.CrossRefPubMedPubMedCentral

74.

Luderer HF, Nazarian RM, Zhu ED, Demay MB. Ligand-dependent actions of the vitamin D receptor are required for activation of TGF-β signaling during the inflammatory response to cutaneous injury. 2013;154(1):16-24. doi: https://doi.org/10.1210/en.2012-1579.

75.

Proudfoot D. Calcium signaling and tissue calcification. Cold Spring Harb Perspect Biol. 2019;11(10):a035303. https://doi.org/10.1101/cshperspect.a035303.CrossRefPubMed

76.

Pal SN, Golledge J. Osteo-progenitors in vascular calcification. J Atheroscler Thromb. 2010;18(7):551–9. https://doi.org/10.5551/jat.8656.CrossRef

77.

Rattazzi M, Faggin E, Buso R, Di Virgilio R, Puato M, Plebani M, et al. Atorvastatin reduces circulating osteoprogenitor cells and T-cell RANKL expression in osteoporotic women: implications for the bone-vascular axis. Cardiovasc Ther. 2016;34(1):13–20. https://doi.org/10.1111/1755-5922.12163.CrossRefPubMed

78.

Ma L, Ishigami M, Honda T, Yokoyama S, Yamamoto K, Ishizu Y, et al. Antifibrotic effects of 1,25(OH)2D3 on nonalcoholic steatohepatitis in female mice. Dig Dis Sci. 2019;64(9):2581–90. https://doi.org/10.1007/s10620-019-05560-3.CrossRefPubMed

79.

Hou YC, Lu CL, Zheng CM, Liu WC, Yen TH, Chen RM, et al. The role of vitamin D in modulating mesenchymal stem cells and endothelial progenitor cells for vascular calcification. Int J Mol Sci. 2020;21(7). https://doi.org/10.3390/ijms21072466.

80.

McCabe KM, Zelt JG, Kaufmann M, Laverty K, Ward E, Barron H, et al. Calcitriol accelerates vascular calcification irrespective of vitamin K status in a rat model of chronic kidney disease with hyperphosphatemia and secondary hyperparathyroidism. J Pharmacol Exp Ther. 2018;366(3):433–45. https://doi.org/10.1124/jpet.117.247270.CrossRefPubMed

81.

Orfanidou T, Malizos KN, Varitimidis S, Tsezou A. 1,25-Dihydroxyvitamin D(3) and extracellular inorganic phosphate activate mitogen-activated protein kinase pathway through fibroblast growth factor 23 contributing to hypertrophy and mineralization in osteoarthritic chondrocytes. Exp Biol Med (Maywood). 2012;237(3):241–53. https://doi.org/10.1258/ebm.2011.011301.CrossRef

82.

Mizobuchi M, Ogata H, Koiwa F, Kinugasa E, Akizawa T. Vitamin D and vascular calcification in chronic kidney disease. Bone. 2009;45(Suppl 1):S26–9. https://doi.org/10.1016/j.bone.2009.01.011.CrossRefPubMed

83.

Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 1997;96(6):1755–60. https://doi.org/10.1161/01.cir.96.6.1755.CrossRefPubMed

84.

Pirro M, Manfredelli MR, Schillaci G, Helou RS, Bagaglia F, Melis F, et al. Association between circulating osteoblast progenitor cells and aortic calcifications in women with postmenopausal osteoporosis. Nutr Metab Cardiovasc Dis. 2013;23(5):466–72. https://doi.org/10.1016/j.numecd.2011.08.006.CrossRefPubMed

85.

Han MS, Che X, Cho GH, Park HR, Lim KE, Park NR, et al. Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification. PLoS One. 2013;8(12):e83584. https://doi.org/10.1371/journal.pone.0083584.CrossRefPubMedPubMedCentral

86.

Martineau C, Naja RP, Husseini A, Hamade B, Kaufmann M, Akhouayri O, et al. Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2. J Clin Investig. 2018;128(8):3546–57. https://doi.org/10.1172/jci98093.CrossRefPubMedPubMedCentral

87.

Lee S-H, Agashe MV, Suh S-W, Yoon Y-C, Song S-H, Yang J-H, et al. Paravertebral ligament ossification in vitamin D–resistant rickets. Spine. 2012;37(13):E792–E6. https://doi.org/10.1097/brs.0b013e31824a3dc8.CrossRefPubMed

88.

Oleson CV, Seidel BJ, Zhan T. Association of vitamin D deficiency, secondary hyperparathyroidism, and heterotopic ossification in spinal cord injury. J Rehabil Res Dev. 2013;50(9):1177–86. https://doi.org/10.1682/jrrd.2012.11.0206.CrossRefPubMed

89.

Ekiz T, Demir S, Doĝan A, Özgigin N. Coexistence of heterotopic ossification of the elbow and vitamin D deficiency following stroke: can calcium and vitamin D treatment aggravate ossification? West Indian Med J. 2014. https://doi.org/10.7727/wimj.2014.076.

90.

Hongwei M, Tiebing Q, Zhiguo L, Kemin L. Proteomics study on biomarkers for heterotopic ossification secondary to traumatic brain injuries. J Rehabil Med. 2020;52(1):1–7. https://doi.org/10.2340/16501977-2622.CrossRef

91.

Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, et al. Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem. 2009;284(11):7149–56. https://doi.org/10.1074/jbc.M801681200.CrossRefPubMedPubMedCentral

92.

Xiao HQ, Shi W, Liu SX, Zhang B, Xu LX, Liang XL, et al. Podocyte injury is suppressed by 1,25-dihydroxyvitamin D via modulation of transforming growth factor-beta 1/bone morphogenetic protein-7 signalling in puromycin aminonucleoside nephropathy rats. Clin Exp Pharmacol Physiol. 2009;36(7):682–9. https://doi.org/10.1111/j.1440-1681.2008.05133.x.CrossRefPubMed

93.

Li A, Cong Q, Xia X, Leong WF, Yeh J, Miao D, et al. Pharmacologic calcitriol inhibits osteoclast lineage commitment via the BMP-Smad1 and IκB-NF-κB pathways. J Bone Miner Res. 2017;32(7):1406–20. https://doi.org/10.1002/jbmr.3146.CrossRefPubMed

94.

Al Saedi A, Myers D, Stupka N, Duque G. 1,25(OH)(2)D(3) ameliorates palmitate-induced lipotoxicity in human primary osteoblasts leading to improved viability and function. Bone. 2020;115672:115672. https://doi.org/10.1016/j.bone.2020.115672.CrossRef

Titel: Do Interactions of Vitamin D3 and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva?
verfasst von: Jessica L. Pierce
Daniel S. Perrien
Publikationsdatum: 14.04.2021
Verlag: Springer US
Erschienen in: Current Osteoporosis Reports / Ausgabe 3/2021
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-021-00673-z

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Knie-TEP: Kein Vorteil durch antibiotikahaltigen Knochenzement

29.05.2024 Periprothetische Infektionen Nachrichten

Zur Zementierung einer Knie-TEP wird in Deutschland zu über 98% Knochenzement verwendet, der mit einem Antibiotikum beladen ist. Ob er wirklich besser ist als Zement ohne Antibiotikum, kann laut Registerdaten bezweifelt werden.

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

28.05.2024 Häusliche Gewalt Nachrichten

In der Notaufnahme wird die Chance, Opfer von häuslicher Gewalt zu identifizieren, von Orthopäden und Orthopädinnen offenbar zu wenig genutzt. Darauf deuten die Ergebnisse einer Fragebogenstudie an der Sahlgrenska-Universität in Schweden hin.

Fehlerkultur in der Medizin – Offenheit zählt!

28.05.2024 Fehlerkultur Podcast

Darüber reden und aus Fehlern lernen, sollte das Motto in der Medizin lauten. Und zwar nicht nur im Sinne der Patientensicherheit. Eine negative Fehlerkultur kann auch die Behandelnden ernsthaft krank machen, warnt Prof. Dr. Reinhard Strametz. Ein Plädoyer und ein Leitfaden für den offenen Umgang mit kritischen Ereignissen in Medizin und Pflege.

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Do Interactions of Vitamin D₃ and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva?

Abstract

Purpose of Review

Recent Findings

Summary

Arthropedia

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Knie-TEP: Kein Vorteil durch antibiotikahaltigen Knochenzement

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

Fehlerkultur in der Medizin – Offenheit zählt!

Mehr Frauen im OP – weniger postoperative Komplikationen

Update Orthopädie und Unfallchirurgie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2021

The Gut Microbiome: a New Frontier in Musculoskeletal Research

Part 2: When Should Bisphosphonates Be Used in Children with Chronic Illness Osteoporosis?

Current Analysis of Skeletal Phenotypes in Down Syndrome

MicroRNAs and Their Roles in Breast Cancer Bone Metastasis

Preventing Bone Stress Injuries in Runners with Optimal Workload

Genetic Determinants of Paget’s Disease of Bone

Arthropedia

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Knie-TEP: Kein Vorteil durch antibiotikahaltigen Knochenzement

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

Fehlerkultur in der Medizin – Offenheit zählt!

Mehr Frauen im OP – weniger postoperative Komplikationen

Update Orthopädie und Unfallchirurgie