RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp.
Animals
Biomarkers
Cell Differentiation
Cellular Microenvironment
/ genetics
Dental Pulp
/ metabolism
Fluorescent Antibody Technique
/ methods
Gene Expression
Immunohistochemistry
Mice
Models, Biological
Odontogenesis
/ genetics
Osteoclasts
/ metabolism
Osteoprotegerin
/ metabolism
RANK Ligand
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 02 2021
25 02 2021
Historique:
received:
07
11
2020
accepted:
16
02
2021
entrez:
26
2
2021
pubmed:
27
2
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of OPG-deficient (KO) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in OPG-KO mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.
Identifiants
pubmed: 33633362
doi: 10.1038/s41598-021-84354-y
pii: 10.1038/s41598-021-84354-y
pmc: PMC7907144
doi:
Substances chimiques
Biomarkers
0
Osteoprotegerin
0
RANK Ligand
0
Tnfrsf11b protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4575Références
Martin, T. J., Romas, E. & Gillespie, M. T. Interleukins in the control of osteoclast differentiation. Crit. Rev. Eukaryot. Gene Expr. 8, 107–123 (1998).
pubmed: 9714893
doi: 10.1615/CritRevEukarGeneExpr.v8.i2.10
Roodman, G. D. Cell biology of the osteoclast. Exp. Hematol. 27, 1229–1241 (1999).
pubmed: 10428500
doi: 10.1016/S0301-472X(99)00061-2
Chambers, T. J. Regulation of the differentiation and function of osteoclasts. J. Pathol. 192, 4–13 (2000).
pubmed: 10951393
doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH645>3.0.CO;2-Q
Boyle, W. J., Simonet, W. S. & Lacey, D. L. Osteoclast differentiation and activation. Nature 423, 337–342 (2003).
pubmed: 12748652
doi: 10.1038/nature01658
Suda, T. et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev. 20, 345–357 (1999).
pubmed: 10368775
doi: 10.1210/edrv.20.3.0367
Nakashima, T., Hayashi, M. & Takayanagi, H. New insights into osteoclastogenic signaling mechanisms. Trends Endocrinol. Metab. 23, 582–590 (2012).
pubmed: 22705116
doi: 10.1016/j.tem.2012.05.005
Oshiro, T., Shibasaki, Y., Martin, T. J. & Sasaki, T. Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts during physiological root resorption of human deciduous teeth. Anat. Rec. 264, 305–311 (2001).
pubmed: 11596012
doi: 10.1002/ar.1127
Sasaki, T. Differentiation and functions of osteoclasts and odontoclasts in mineralized tissue resorption. Microsc. Res. Tech. 61, 483–495 (2003).
pubmed: 12879416
doi: 10.1002/jemt.10370
Wedenberg, C. & Lindskog, S. Experimental internal resorption in monkey teeth. Endod. Dent. Traumatol. 1, 221–227 (1985).
pubmed: 2868886
doi: 10.1111/j.1600-9657.1985.tb00584.x
Wedenberg, C. & Zetterqvist, L. Internal resorption in human teeth-a histological, scanning electron microscopic, and enzyme histochemical study. J. Endod. 13, 255–259 (1987).
pubmed: 3474343
doi: 10.1016/S0099-2399(87)80041-9
Andreasen, J. O. & Andreasen, F. M. Root resorption following traumatic dental injuries. Proc. Finn. Dent. Soc. 88(Suppl 1), 95–114 (1992).
pubmed: 1354871
Sahara, N. et al. Odontoclastic resorption at the pulpal surface of coronal dentin prior to the shedding of human deciduous teeth. Arch. Histol. Cytol. 55, 273–285 (1992).
pubmed: 1419277
doi: 10.1679/aohc.55.273
Gunraj, M. N. Dental root resorption. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 88, 647–653 (1999).
pubmed: 10625842
doi: 10.1016/S1079-2104(99)70002-8
Hargreaves, K. M., Tay, F. R., Seltzer, S. & Goodis, H. E. Seltzer and Bender’s dental pulp 2nd edn. (Quintessence, Berlin, 2012).
Rani, C. S. & MacDougall, M. Dental cells express factors that regulate bone resorption. Mol. Cell Biol. Res. Commun. 3, 145–152 (2000).
pubmed: 10860862
doi: 10.1006/mcbr.2000.0205
Lossdorfer, S., Gotz, W. & Jager, A. Immunohistochemical localization of receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth. Calcif. Tissue Int. 71, 45–52 (2002).
pubmed: 12043011
doi: 10.1007/s00223-001-2086-7
Fukushima, H., Kajiya, H., Takada, K., Okamoto, F. & Okabe, K. Expression and role of RANKL in periodontal ligament cells during physiological root-resorption in human deciduous teeth. Eur. J. Oral Sci. 111, 346–352 (2003).
pubmed: 12887401
doi: 10.1034/j.1600-0722.2003.00051.x
Uchiyama, M. et al. Dental pulp and periodontal ligament cells support osteoclastic differentiation. J. Dent. Res. 88, 609–614 (2009).
pubmed: 19641147
doi: 10.1177/0022034509340008
Iwasaki, Y. et al. In situ proliferation and differentiation of macrophages in dental pulp. Cell Tissue Res. 346, 99–109 (2011).
pubmed: 21922246
pmcid: 3204101
doi: 10.1007/s00441-011-1231-5
Heyeraas, K. J. & Berggreen, E. Interstitial fluid pressure in normal and inflamed pulp. Crit. Rev. Oral Biol. Med. 10, 328–336 (1999).
pubmed: 10759412
doi: 10.1177/10454411990100030501
Rombouts, C., Giraud, T., Jeanneau, C. & About, I. Pulp vascularization during tooth development, regeneration, and therapy. J. Dent. Res. 96, 137–144 (2017).
pubmed: 28106505
doi: 10.1177/0022034516671688
Mavridou, A. M. et al. Is hypoxia related to external cervical resorption? A case report. J. Endod. 45, 459–470 (2019).
pubmed: 30771897
doi: 10.1016/j.joen.2018.12.013
Kato, R. et al. Gap-junction-mediated communication in human periodontal ligament cells. J. Dent. Res. 92, 635–640 (2013).
pubmed: 23677649
doi: 10.1177/0022034513489992
Zhu, J. et al. HIF-1alpha facilitates osteocyte-mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro. J. Cell Physiol. 234, 21182–21192 (2019).
pubmed: 31032948
doi: 10.1002/jcp.28721
Lee, S. Y. et al. Controlling hypoxia-inducible factor-2alpha is critical for maintaining bone homeostasis in mice. Bone Res. 7, 14 (2019).
pubmed: 31098335
pmcid: 6513851
doi: 10.1038/s41413-019-0054-y
Ryu, J. H. et al. Hypoxia-inducible factor-2alpha is an essential catabolic regulator of inflammatory rheumatoid arthritis. PLoS Biol 12, e1001881 (2014).
pubmed: 24914685
pmcid: 4051611
doi: 10.1371/journal.pbio.1001881
Zheng, Y. et al. Mesenchymal dental pulp cells attenuate dentin resorption in homeostasis. J. Dent. Res. 94, 821–827 (2015).
pubmed: 25762594
pmcid: 4485326
doi: 10.1177/0022034515575347
Bucay, N. et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12, 1260–1268 (1998).
pubmed: 9573043
pmcid: 316769
doi: 10.1101/gad.12.9.1260
Mizuno, A. et al. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res. Commun. 247, 610–615 (1998).
pubmed: 9647741
doi: 10.1006/bbrc.1998.8697
Rossert, J., Eberspaecher, H. & de Crombrugghe, B. Separate cis-acting DNA elements of the mouse pro-alpha 1(I) collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice. J. Cell Biol. 129, 1421–1432 (1995).
pubmed: 7775585
doi: 10.1083/jcb.129.5.1421
Nakamura, M. et al. Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption. Endocrinology 144, 5441–5449 (2003).
pubmed: 14500574
doi: 10.1210/en.2003-0717
Matsuo, K. et al. Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus. Development 142, 3912–3920 (2015).
pubmed: 26428006
pmcid: 4712877
Tsukamoto-Tanaka, H., Ikegame, M., Takagi, R., Harada, H. & Ohshima, H. Histochemical and immunocytochemical study of hard tissue formation in dental pulp during the healing process in rat molars after tooth replantation. Cell Tissue Res. 325, 219–229 (2006).
pubmed: 16596394
doi: 10.1007/s00441-005-0138-4
Unno, H., Suzuki, H., Nakakura-Ohshima, K., Jung, H. S. & Ohshima, H. Pulpal regeneration following allogenic tooth transplantation into mouse maxilla. Anat. Rec. 292, 570–579 (2009).
doi: 10.1002/ar.20831
Harokopakis-Hajishengallis, E. Physiologic root resorption in primary teeth: molecular and histological events. J. Oral Sci. 49, 1–12 (2007).
pubmed: 17429176
doi: 10.2334/josnusd.49.1
Zhang, J. et al. The existence of CD11c+ sentinel and F4/80+ interstitial dendritic cells in dental pulp and their dynamics and functional properties. Int. Immunol. 18, 1375–1384 (2006).
pubmed: 16849394
doi: 10.1093/intimm/dxl070
Mizoguchi, T. et al. Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. J. Cell Biol. 184, 541–554 (2009).
pubmed: 19237598
pmcid: 2654120
doi: 10.1083/jcb.200806139
Muto, A. et al. Lineage-committed osteoclast precursors circulate in blood and settle down into bone. J. Bone Miner. Res. 26, 2978–2990 (2011).
pubmed: 21898588
doi: 10.1002/jbmr.490
Nakamichi, Y. et al. Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice. Proc. Natl. Acad. Sci. 109, 10006–10011 (2012).
pubmed: 22670054
doi: 10.1073/pnas.1207361109
pmcid: 3382519
Yahara, Y. et al. Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair. Nat. Cell Biol. 22, 49–59 (2020).
pubmed: 31907410
pmcid: 6953622
doi: 10.1038/s41556-019-0437-8
Udagawa, N., Kotake, S., Kamatani, N., Takahashi, N. & Suda, T. The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. Arthritis Res. 4, 281–289 (2002).
pubmed: 12223101
pmcid: 128939
doi: 10.1186/ar431
Tsukasaki, M. & Takayanagi, H. Osteoimmunology: evolving concepts in bone-immune interactions in health and disease. Nat. Rev. Immunol. 19, 626–642 (2019).
pubmed: 31186549
doi: 10.1038/s41577-019-0178-8
Jontell, M., Okiji, T., Dahlgren, U. & Bergenholtz, G. Immune defense mechanisms of the dental pulp. Crit. Rev. Oral Biol. Med. 9, 179–200 (1998).
pubmed: 9603235
doi: 10.1177/10454411980090020301
Takahashi, N. et al. Osteoblastic cells are involved in osteoclast formation. Endocrinology 123, 2600–2602 (1988).
pubmed: 2844518
doi: 10.1210/endo-123-5-2600