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Published in: Virchows Archiv 5/2013

01-05-2013 | Original Article

Dentine matrix protein 1 (DMP-1) is a marker of bone-forming tumours

Authors: T. G. Kashima, A. Dongre, U. Oppermann, N. A. Athanasou

Published in: Virchows Archiv | Issue 5/2013

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Abstract

Dentin matrix protein 1 (DMP-1) is highly expressed by osteocytes and is a non-collagenous matrix protein found in dentin and bone. In this study, we determined the expression of DMP-1 in mature and immature human bone and examined whether DMP-1 is useful in distinguishing osteoid/bone-forming tumours from other primary and secondary bone tumours. DMP-1 expression was immunohistochemically determined in paraffin sections of a wide range of benign and malignant primary bone tumours and tumour-like lesions (n = 353). DMP-1 mRNA expression was also examined in osteosarcoma and fibrosarcoma cell lines as well as bone tumour specimens (n = 5) using real-time PCR. In lamellar and woven bone, DMP-1 was expressed in the matrix around osteocyte lacunae and canaliculi; osteoblasts and other cell types in the bone were negative. Matrix staining of the osteoid and bone was seen in bone-forming tumours including osteoma, osteoid osteoma, osteoblastoma and osteosarcoma. DMP-1 staining was also seen in fibrous dysplasia, osteofibrous dysplasia and chondroblastoma and in reactive bone in solitary bone cysts and aneurysmal bone cysts. DMP-1 was not expressed in the tumour component of other bone neoplasms including Ewing sarcoma, chondrosarcoma, leiomyosarcoma, fibrosarcoma, giant cell tumour of bone and metastatic carcinoma. DMP-1 mRNA was expressed in osteosarcoma cell lines and tumour samples. DMP-1 is a matrix marker expressed around osteocytes in human woven and lamellar bone and is useful in identifying osteosarcoma and other bone-forming tumours.
Literature
1.
go back to reference Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedCrossRef Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedCrossRef
2.
go back to reference Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235:176–190PubMedCrossRef Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235:176–190PubMedCrossRef
3.
go back to reference Bonewald L (2007) Osteocytes. In: Marcus D, Nelson D, Rosen C (eds) Osteoporosis. Elsevier, San Diego, pp 169–190 Bonewald L (2007) Osteocytes. In: Marcus D, Nelson D, Rosen C (eds) Osteoporosis. Elsevier, San Diego, pp 169–190
4.
go back to reference Palumbo C, Palazzini S, Marotti G (1990) Morphological study of intercellular junctions during osteocyte differentiation. Bone 11:401–406PubMedCrossRef Palumbo C, Palazzini S, Marotti G (1990) Morphological study of intercellular junctions during osteocyte differentiation. Bone 11:401–406PubMedCrossRef
5.
go back to reference Ling Y, Rios HF, Myers ER, Lu Y, Feng JQ, Boskey AL (2005) DMP1 depletion decreases done mineralization in vivo: an FTIR imaging analysis. J Bone Miner Res 20:2169–2177PubMedCrossRef Ling Y, Rios HF, Myers ER, Lu Y, Feng JQ, Boskey AL (2005) DMP1 depletion decreases done mineralization in vivo: an FTIR imaging analysis. J Bone Miner Res 20:2169–2177PubMedCrossRef
6.
go back to reference Tanaka K, Yamaguchi Y, Hakeda Y (1995) Isolated chick osteocytes stimulate formation and bone-resorbing activity of osteoclast-like cells. J Bone Miner Metab 13:61–70CrossRef Tanaka K, Yamaguchi Y, Hakeda Y (1995) Isolated chick osteocytes stimulate formation and bone-resorbing activity of osteoclast-like cells. J Bone Miner Metab 13:61–70CrossRef
7.
go back to reference Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241PubMedCrossRef Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241PubMedCrossRef
9.
go back to reference Narayanan K, Ramachandran A, Hao J, He G, Park KW, Cho M, George A (2003) Dual functional roles of dentin matrix protein 1. Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store. J Biol Chem 278:17500–17508PubMedCrossRef Narayanan K, Ramachandran A, Hao J, He G, Park KW, Cho M, George A (2003) Dual functional roles of dentin matrix protein 1. Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store. J Biol Chem 278:17500–17508PubMedCrossRef
10.
go back to reference Dallas SL, Bonewald LF (2010) Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci 1192:437–443PubMedCrossRef Dallas SL, Bonewald LF (2010) Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci 1192:437–443PubMedCrossRef
11.
go back to reference Eapen A, Sundivakkam P, Song Y, Ravindran S, Ramachandran A, Tiruppathi C, George A (2010) Calcium-mediated stress kinase activation by DMP1 promotes osteoblast differentiation. J Biol Chem 285:36339–36351PubMedCrossRef Eapen A, Sundivakkam P, Song Y, Ravindran S, Ramachandran A, Tiruppathi C, George A (2010) Calcium-mediated stress kinase activation by DMP1 promotes osteoblast differentiation. J Biol Chem 285:36339–36351PubMedCrossRef
12.
go back to reference Narayanan K, Ramachandran A, Hao J, George A (2002) Transcriptional regulation of dentin matrix protein 1 (DMP1) by AP-1 (c-fos/c-jun) factors. Connect Tissue Res 43:365–371PubMed Narayanan K, Ramachandran A, Hao J, George A (2002) Transcriptional regulation of dentin matrix protein 1 (DMP1) by AP-1 (c-fos/c-jun) factors. Connect Tissue Res 43:365–371PubMed
13.
go back to reference Gajjeraman S, Narayanan K, Hao J, Qin C, George A (2007) Matrix macromolecules in hard tissues control the nucleation and hierarchical assembly of hydroxyapatite. J Biol Chem 282:1193–1204PubMedCrossRef Gajjeraman S, Narayanan K, Hao J, Qin C, George A (2007) Matrix macromolecules in hard tissues control the nucleation and hierarchical assembly of hydroxyapatite. J Biol Chem 282:1193–1204PubMedCrossRef
14.
go back to reference Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE (2006) Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 38:1310–1315PubMedCrossRef Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE (2006) Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 38:1310–1315PubMedCrossRef
15.
go back to reference Lorenz-Depiereux B, Bastepe M, Benet-Pagès A, Amyere M, Wagenstaller J, Müller-Barth U, Badenhoop K, Kaiser S, Rittmaster R, Shlossberg A (2006) DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 38:1248–1250PubMedCrossRef Lorenz-Depiereux B, Bastepe M, Benet-Pagès A, Amyere M, Wagenstaller J, Müller-Barth U, Badenhoop K, Kaiser S, Rittmaster R, Shlossberg A (2006) DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 38:1248–1250PubMedCrossRef
16.
go back to reference Fletcher C, Unni K, Mertens F (2002) Tumours of soft tissue and bone. IARC, Lyon Fletcher C, Unni K, Mertens F (2002) Tumours of soft tissue and bone. IARC, Lyon
17.
go back to reference Jaffe HL (1958) Tumors and tumorous conditions of the bones and joints. Lea and Febiger, Philadelphia Jaffe HL (1958) Tumors and tumorous conditions of the bones and joints. Lea and Febiger, Philadelphia
18.
go back to reference Gao Z, Kahn LB (2005) The application of immunohistochemistry in the diagnosis of bone tumors and tumor-like lesions. Skeletal Radiol 34:755–770PubMedCrossRef Gao Z, Kahn LB (2005) The application of immunohistochemistry in the diagnosis of bone tumors and tumor-like lesions. Skeletal Radiol 34:755–770PubMedCrossRef
19.
go back to reference Pereira RC, Jüppner H, Azucena-Serrano CE, Yadin O, Salusky IB, Wesseling-Perry K (2009) Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease. Bone 45:1161–1168PubMedCrossRef Pereira RC, Jüppner H, Azucena-Serrano CE, Yadin O, Salusky IB, Wesseling-Perry K (2009) Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease. Bone 45:1161–1168PubMedCrossRef
20.
go back to reference Toyosawa S, Shintani S, Fujiwara T, Ooshima T, Sato A, Ijuhin N, Komori T (2001) Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Miner Res 16:2017–2026PubMedCrossRef Toyosawa S, Shintani S, Fujiwara T, Ooshima T, Sato A, Ijuhin N, Komori T (2001) Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Miner Res 16:2017–2026PubMedCrossRef
21.
go back to reference Ferrera D, Poggi S, Biassoni C, Dickson GR, Astigiano S, Barbieri O, Favre A, Franzi AT, Strangio A, Federici A, Manduca P (2002) Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice. Bone 30:718–725PubMedCrossRef Ferrera D, Poggi S, Biassoni C, Dickson GR, Astigiano S, Barbieri O, Favre A, Franzi AT, Strangio A, Federici A, Manduca P (2002) Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice. Bone 30:718–725PubMedCrossRef
22.
go back to reference Serra M, Scotlandi K, Sollazzo M, Sarti M, Maurici D, Benini S, Picci P, Bertoni F, Baldini N (1996) Value of immunohistochemical detection of noncollagenous proteins of bone for the diagnosis of bone tumours. Int J Oncol 9:257–261PubMed Serra M, Scotlandi K, Sollazzo M, Sarti M, Maurici D, Benini S, Picci P, Bertoni F, Baldini N (1996) Value of immunohistochemical detection of noncollagenous proteins of bone for the diagnosis of bone tumours. Int J Oncol 9:257–261PubMed
23.
go back to reference Tartaix PH, Doulaverakis M, George A, Fisher LW, Butler WT, Qin C, Salih E, Tan M, Fujimoto Y, Spevak L, Boskey AL (2004) In vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions. J Biol Chem 279:18115–18120PubMedCrossRef Tartaix PH, Doulaverakis M, George A, Fisher LW, Butler WT, Qin C, Salih E, Tan M, Fujimoto Y, Spevak L, Boskey AL (2004) In vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions. J Biol Chem 279:18115–18120PubMedCrossRef
24.
go back to reference Toyosawa S, Kanatani N, Shintani S, Kobata M, Yuki M, Kishino M, Ijuhin N, Komori T (2004) Expression of dentin matrix protein 1 (DMP1) during fracture healing. Bone 35:553–561PubMedCrossRef Toyosawa S, Kanatani N, Shintani S, Kobata M, Yuki M, Kishino M, Ijuhin N, Komori T (2004) Expression of dentin matrix protein 1 (DMP1) during fracture healing. Bone 35:553–561PubMedCrossRef
25.
go back to reference Hughes F, Aubin J (1997) Culture of cells of the osteoblast linage. In: Arnett T, Henderson B (eds) Methods in bone biology. Chapman & Hall Ltd, London, p 33 Hughes F, Aubin J (1997) Culture of cells of the osteoblast linage. In: Arnett T, Henderson B (eds) Methods in bone biology. Chapman & Hall Ltd, London, p 33
26.
go back to reference Midura RJ, Midura SB, Su X, Gorski JP (2011) Separation of newly formed bone from older compact bone reveals clear compositional differences in bone matrix. Bone 49:1365–1374PubMedCrossRef Midura RJ, Midura SB, Su X, Gorski JP (2011) Separation of newly formed bone from older compact bone reveals clear compositional differences in bone matrix. Bone 49:1365–1374PubMedCrossRef
27.
go back to reference Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, Pavlin D (2003) Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. J Bone Miner Res 18:807–817PubMedCrossRef Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, Pavlin D (2003) Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. J Bone Miner Res 18:807–817PubMedCrossRef
28.
go back to reference Toyosawa S, Yuki M, Kishino M, Ogawa Y, Ueda T, Murakami S, Konishi E, Iida S, Kogo M, Komori T (2007) Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol 20:389–396PubMedCrossRef Toyosawa S, Yuki M, Kishino M, Ogawa Y, Ueda T, Murakami S, Konishi E, Iida S, Kogo M, Komori T (2007) Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol 20:389–396PubMedCrossRef
29.
go back to reference Mirra J (1989) Bone tumours: clinical, radiologic and pathological correlation. Lea and Febiger, Philadelphia Mirra J (1989) Bone tumours: clinical, radiologic and pathological correlation. Lea and Febiger, Philadelphia
30.
go back to reference Aigner T, Loos S, Inwards C, Perris R, Perissinotto D, Unni KK, Kirchner T (1999) Chondroblastoma is an osteoid-forming, but not cartilage-forming neoplasm. J Pathol 189:463–469PubMedCrossRef Aigner T, Loos S, Inwards C, Perris R, Perissinotto D, Unni KK, Kirchner T (1999) Chondroblastoma is an osteoid-forming, but not cartilage-forming neoplasm. J Pathol 189:463–469PubMedCrossRef
31.
go back to reference Konishi E, Nakashima Y, Iwasa Y, Nakao R, Yanagisawa A (2010) Immunohistochemical analysis for Sox9 reveals the cartilaginous character of chondroblastoma and chondromyxoid fibroma of the bone. Hum Pathol 41:208–213PubMedCrossRef Konishi E, Nakashima Y, Iwasa Y, Nakao R, Yanagisawa A (2010) Immunohistochemical analysis for Sox9 reveals the cartilaginous character of chondroblastoma and chondromyxoid fibroma of the bone. Hum Pathol 41:208–213PubMedCrossRef
32.
go back to reference Romeo S, Oosting J, Rozeman LB, Hameetman L, Taminiau AH, Cleton-Jansen AM, Bovee JV, Hogendoorn PCW (2007) The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma. Cancer 110:385–394PubMedCrossRef Romeo S, Oosting J, Rozeman LB, Hameetman L, Taminiau AH, Cleton-Jansen AM, Bovee JV, Hogendoorn PCW (2007) The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma. Cancer 110:385–394PubMedCrossRef
Metadata
Title
Dentine matrix protein 1 (DMP-1) is a marker of bone-forming tumours
Authors
T. G. Kashima
A. Dongre
U. Oppermann
N. A. Athanasou
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 5/2013
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-013-1399-z

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