BRONJ-related jaw bone is associated with increased Dlx-5 and suppressed osteopontin—implication in the site-specific alteration of angiogenesis and bone turnover by bisphosphonates

详细信息    查看全文

• 作者：Falk Wehrhan ; Kerstin Amann ; Patrick M?bius ; Manuel Weber…
• 关键词：BRONJ ; Dlx ; 5 ; Osteopontin ; Immunohistochemistry ; mRNA ; Bisphosphonate
• 刊名：Clinical Oral Investigations
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：19
• 期：6
• 页码：1289-1298
• 全文大小：812 KB
• 参考文献：1.Abu-Id MH, Warnke PH, Gottschalk J et al (2008) “Bis-phossy jaws”—high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg 36:95-03PubMed View Article
  2.Acampora D, Merlo GR, Paleari L et al (1999) Craniofacial, vestibular and bone defects in mice lacking the distal-less-related gene Dlx5. Development 126:3795-809PubMed
  3.Alford AI, Hankenson KD (2006) Matricellular proteins: extracellular modulators of bone development, remodeling, and regeneration. Bone 38:749-57PubMed View Article
  4.Asou Y, Rittling SR, Yoshitake H et al (2001) Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone. Endocrinology 142:1325-332PubMed
  5.Babajko S, Meary F, Petit S et al (2011) Transcriptional regulation of MSX1 natural antisense transcript. Cells Tissues Organs 194:151-55PubMed View Article
  6.Babajko S, Petit S, Fernandes I et al (2009) Msx1 expression regulation by its own antisense RNA: consequence on tooth development and bone regeneration. Cells Tissues Organs 189:115-21PubMed View Article
  7.Berdal A, Lezot F, Nefussi JR et al (2000) Mineralized dental tissues: a unique example of skeletal biodiversity derived from cephaic neural crest. Morphologie 84:5-0PubMed
  8.Berdal A, Molla M, Hotton D et al (2009) Differential impact of MSX1 and MSX2 homeogenes on mouse maxillofacial skeleton. Cells Tissues Organs 189:126-32PubMed View Article
  9.Blum A, Zarqh O, Peleg A et al (2012) Vascular inflammation and endothelial dysfunction in fracture healing. Am J Orthop (Belle Mead NJ) 41:87-1
  10.Boskey AL, Spevak L, Paschalis E et al (2002) Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone. Calcif Tissue Int 71:145-54PubMed View Article
  11.Cardemil C, Omar OM, Norlindh B et al (2013) The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model. Biomaterials 34:1546-561PubMed View Article
  12.Das S, Edwards PA, Crockett JC et al (2014) Upregulation of endogenous farnesyl diphosphate synthase overcomes the inhibitory effect of bisphosphonate on protein prenylation in hela cells. Biochim Biophys Acta 1841:569-73PubMed View Article
  13.Depew MJ, Liu JK, Long JE et al (1999) Dlx5 regulates regional development of the branchial arches and sensory capsules. Development 126:3831-846PubMed
  14.Dodds RA, Connor JR, James IE et al (1995) Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: an in vitro and ex vivo study of remodeling bone. J Bone Miner Res 10:1666-680PubMed View Article
  15.Duvall CL, Taylor WR, Weiss D et al (2007) Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice. J Bone Miner Res 22:286-97PubMed View Article
  16.Favia G, Pilolli GP, Maiorano E (2009) Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: an analysis of 31 cases with confocal laser scanning microscopy. Bone 45(3):406-13. doi:10.-016/?j.?bone.-009.-5.-08
  17.Fazzalari NL, Kuliwaba JS, Atkins GJ et al (2001) The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J Bone Miner Res 16:1015-027PubMed View Article
  18.Hassan MQ, Tare RS, Lee SH et al (2006) BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem 281:40515-0526PubMed View Article
  19.Holleville N, Quilhac A, Bontoux M et al (2003) BMP signals regulate Dlx5 during early avian skull development. Dev Biol 257:177-89PubMed View Article
  20.Houpis CH, Tosios KI, Papavasileiou D et al (2010) Parathyroid hormone-related peptide (PTHrP), parathyroid hormone/parathyroid hormone-related peptide receptor 1 (PTHR1), and MSX1 protein are expressed in central and peripheral giant cell granulomas of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(3):415-24. doi:10.-016/?j.?tripleo.-009.-9.-26
  21.Hunter GK, Hauschka PV, Poole AR et al (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochemical j 317(1):59-4
  22.Jacobs C, Walter C, Ziebart T et al. (2014) Mechanical loading influences the effects of bisphosphonates on human periodontal ligament fibroblasts. Clin Oral Investig doi:10.-007/?s00784-014-1284-4
  23.Jeong HM, Jin YH, Choi YH et al (2013) Risedronate increases osteoblastic differentiation and function through connexin43. Biochem Biophys Res Commun 432:152-56PubMed View Article
  24.Kaji H, Sugimoto T, Miyauchi A et al (1994) Calcitonin inhibits osteopontin mRNA expression in isolated rabbit osteoclasts. Endocrinology 135:484-87PubMed
  25.Lesclous P (2009) Bisphosphonate-
• 作者单位：Falk Wehrhan (3)
  Kerstin Amann (2)
  Patrick M?bius (1)
  Manuel Weber (1)
  Raimund Preidl (1)
  Jutta Ries (1)
  Phillip Stockmann (1)
  
  3. Department of Oral and Maxillofacial Surgery, Friedrich-Alexander-University of Erlangen, Glueckstrasse 11, 91054, Erlangen, Germany
  2. Department of Nephropathology, Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany
  1. Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany
  
• 刊物类别：Medicine
• 刊物主题：Dentistry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1436-3771

文摘

Objectives Site-specific suppression of bone remodelling has been implicated in bisphosphonate-(BP)-related osteonecrosis of the jaws (BRONJ). Due to the origin of jaw bone from cranial neural crest, osseous differentiation is regulated specifically by the antagonizing BMP-2-downstream-transcription factors Msx-1 and Dlx-5. Osteopontin has been implicated in bone remodelling and angiogenesis. The osteoblast and osteoclast progenitor proliferation mediating Msx-1 has been demonstrated to be suppressed in BRONJ. In vitro BPs were shown to increase Dlx-5 and to suppress osteopontin expression. This study targeted Dlx-5 and osteopontin in BRONJ-related and BP-exposed jaw bone compared with healthy jaw bone samples at protein- and messenger RNA (mRNA) level, since increased Dlx-5 and suppressed osteopontin might account for impaired bone turnover in BRONJ. Materials and methods Fifteen BRONJ-exposed, 15 BP-exposed and 20 healthy jaw bone samples were processed for real-time reverse transcription polymerase chain reaction (RT-PCR) and for immunohistochemistry. Targeting Dlx-5, osteopontin and glyceraldehyde 3-phosphate dehydrogenase mRNA was extracted, quantified by the LabChip-method, followed by quantitative RT-PCR. For immunohistochemistry, an autostaining-based alkaline phosphatase antialkaline phosphatase (APAPP) staining kit was used. Semiquantitative assessment was performed measuring the ratio of stained cells/total number of cells (labelling index, Bonferroni adjustment). Results The labelling index was significant decreased for osteopontin (p-lt;-.017) and significantly increased for Dlx-5 (p-lt;-.021) in BRONJ samples. In BRONJ specimens, a significant fivefold decrease in gene expression for osteopontin (p-lt;-.015) and a significant eightfold increase in Dlx-5 expression (p-lt;-.012) were found. Conclusions BRONJ-related suppression of bone turnover is consistent with increased Dlx-5 expression and with suppression of osteopontin. The BP-related impaired BMP-2–Msx-1–Dlx-5 axis might explain the jaw bone specific alteration by BP. Clinical relevance The findings of this study help to explain the restriction of RONJ to craniofacial bones. BRONJ might serve as a model of disease elucidating the specific signal transduction of neural crest cell-derived bone structures in health and disease.