Skip to main content
Top
Published in: Journal of Bone and Mineral Metabolism 1/2019

01-01-2019 | Original Article

Differential osteopontin expression in human osteoblasts derived from iliac crest and alveolar bone and its role in early stages of angiogenesis

Authors: Martin Wein, Diana Huelter-Hassler, Katja Nelson, Tobias Fretwurst, Susanne Nahles, Guenter Finkenzeller, Brigitte Altmann, Thorsten Steinberg

Published in: Journal of Bone and Mineral Metabolism | Issue 1/2019

Login to get access

Abstract

In our previous study, we revealed significant differences of osteopontin (OPN) gene expression in primary human osteoblasts (HOBs) derived from iliac crest bone (iHOBs) and alveolar bone (aHOBs). The present study aims at assigning this discriminative expression to a possible biologic function. OPN is known to be involved in several pathologic and physiologic processes, among others angiogenesis. Therefore, we studied the reaction of human umbilical vein endothelial cells (HUVECs) to HOB-derived OPN regarding angiogenesis. To this end, human primary explant cultures of both bone entities from ten donors were established. Subsequent transcription analysis detected higher gene expression of OPN in iHOBs compared to aHOBs, thereby confirming the results of our previous study. This difference was particularly apparent when cultures were derived from female donors. Hence, OPN protein expression as well as the angiogenic potential of OPN was analyzed, originating from HOBs of one female donor. In accordance to the gene expression level, secreted OPN was more abundant in the supernatant of iHOBs than in aHOBs. Moreover, secreted OPN was found to stimulate migration of HUVECs, but not proliferation or tube formation. These results indicate an involvement in very early stages of angiogenesis and a functional distinction of OPN from HOBs derived from different bone entities.
Literature
1.
go back to reference Bouleftour W, Juignet L, Bouet G, Granito RN, Vanden-Bossche A, Laroche N, Aubin JE, Lafage-Proust MH, Vico L, Malaval L (2016) The role of the SIBLING, Bone Sialoprotein in skeletal biology—contribution of mouse experimental genetics. Matrix Biol 52–54:60–77CrossRefPubMed Bouleftour W, Juignet L, Bouet G, Granito RN, Vanden-Bossche A, Laroche N, Aubin JE, Lafage-Proust MH, Vico L, Malaval L (2016) The role of the SIBLING, Bone Sialoprotein in skeletal biology—contribution of mouse experimental genetics. Matrix Biol 52–54:60–77CrossRefPubMed
2.
go back to reference Kahles F, Findeisen HM, Bruemmer D (2014) Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab 3:384–393CrossRefPubMedPubMedCentral Kahles F, Findeisen HM, Bruemmer D (2014) Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab 3:384–393CrossRefPubMedPubMedCentral
3.
go back to reference Kunii Y, Niwa S, Hagiwara Y, Maeda M, Seitoh T, Suzuki T (2009) The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems. Med Mol Morphol 42:155–161CrossRefPubMed Kunii Y, Niwa S, Hagiwara Y, Maeda M, Seitoh T, Suzuki T (2009) The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems. Med Mol Morphol 42:155–161CrossRefPubMed
4.
5.
go back to reference Dai J, Peng L, Fan K, Wang H, Wei R, Ji G, Cai J, Lu B, Li B, Zhang D, Kang Y, Tan M, Qian W, Guo Y (2009) Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 28:3412–3422CrossRefPubMed Dai J, Peng L, Fan K, Wang H, Wei R, Ji G, Cai J, Lu B, Li B, Zhang D, Kang Y, Tan M, Qian W, Guo Y (2009) Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 28:3412–3422CrossRefPubMed
6.
go back to reference Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–1239CrossRefPubMed Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–1239CrossRefPubMed
7.
go back to reference Altintas A, Saruhan-Direskeneli G, Benbir G, Demir M, Purisa S (2009) The role of osteopontin: a shared pathway in the pathogenesis of multiple sclerosis and osteoporosis? J Neurol Sci 276:41–44CrossRefPubMed Altintas A, Saruhan-Direskeneli G, Benbir G, Demir M, Purisa S (2009) The role of osteopontin: a shared pathway in the pathogenesis of multiple sclerosis and osteoporosis? J Neurol Sci 276:41–44CrossRefPubMed
8.
go back to reference Geris L, Gerisch A, Sloten JV, Weiner R, Oosterwyck HV (2008) Angiogenesis in bone fracture healing: a bioregulatory model. J Theor Biol 251:137–158CrossRefPubMed Geris L, Gerisch A, Sloten JV, Weiner R, Oosterwyck HV (2008) Angiogenesis in bone fracture healing: a bioregulatory model. J Theor Biol 251:137–158CrossRefPubMed
12.
go back to reference Poggio P, Grau JB, Field BC, Sainger R, Seefried WF, Rizzolio F, Ferrari G (2011) Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls. J Cell Physiol 226:2139–2149CrossRefPubMedPubMedCentral Poggio P, Grau JB, Field BC, Sainger R, Seefried WF, Rizzolio F, Ferrari G (2011) Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls. J Cell Physiol 226:2139–2149CrossRefPubMedPubMedCentral
13.
go back to reference Hahnel A, Wichmann H, Greither T, Kappler M, Wurl P, Kotzsch M, Taubert H, Vordermark D, Bache M (2012) Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients. BMC Cancer 12:131CrossRefPubMedPubMedCentral Hahnel A, Wichmann H, Greither T, Kappler M, Wurl P, Kotzsch M, Taubert H, Vordermark D, Bache M (2012) Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients. BMC Cancer 12:131CrossRefPubMedPubMedCentral
15.
16.
go back to reference He B, Mirza M, Weber GF (2006) An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene 25:2192–2202CrossRefPubMed He B, Mirza M, Weber GF (2006) An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene 25:2192–2202CrossRefPubMed
17.
go back to reference Wein M, Fretwurst T, Nahles S, Duttenhoefer F, Tomakidi P, Steinberg T, Nelson K (2015) Pilot investigation of the molecular discrimination of human osteoblasts from different bone entities. J Craniomaxillofac Surg 43:1487–1493CrossRefPubMed Wein M, Fretwurst T, Nahles S, Duttenhoefer F, Tomakidi P, Steinberg T, Nelson K (2015) Pilot investigation of the molecular discrimination of human osteoblasts from different bone entities. J Craniomaxillofac Surg 43:1487–1493CrossRefPubMed
18.
go back to reference Lee JT, Choi SY, Kim HL, Kim JY, Lee HJ, Kwon TG (2015) Comparison of gene expression between mandibular and iliac bone-derived cells. Clin Oral Investig 19:1223–1233CrossRefPubMed Lee JT, Choi SY, Kim HL, Kim JY, Lee HJ, Kwon TG (2015) Comparison of gene expression between mandibular and iliac bone-derived cells. Clin Oral Investig 19:1223–1233CrossRefPubMed
19.
go back to reference Long F (2012) Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13:27–38CrossRef Long F (2012) Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13:27–38CrossRef
20.
go back to reference Chung IH, Yamaza T, Zhao H, Choung PH, Shi S, Chai Y (2009) Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development. Stem Cells 27:866–877CrossRefPubMedPubMedCentral Chung IH, Yamaza T, Zhao H, Choung PH, Shi S, Chai Y (2009) Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development. Stem Cells 27:866–877CrossRefPubMedPubMedCentral
21.
go back to reference Leucht P, Kim JB, Amasha R, James AW, Girod S, Helms JA (2008) Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration. Development 135:2845–2854CrossRefPubMed Leucht P, Kim JB, Amasha R, James AW, Girod S, Helms JA (2008) Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration. Development 135:2845–2854CrossRefPubMed
22.
go back to reference Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y (2015) The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol 17:386–396CrossRefPubMedPubMedCentral Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y (2015) The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol 17:386–396CrossRefPubMedPubMedCentral
23.
go back to reference Matsuura T, Tokutomi K, Sasaki M, Katafuchi M, Mizumachi E, Sato H (2014) Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry. Biomed Res Int 2014:769414PubMedPubMedCentral Matsuura T, Tokutomi K, Sasaki M, Katafuchi M, Mizumachi E, Sato H (2014) Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry. Biomed Res Int 2014:769414PubMedPubMedCentral
24.
go back to reference Kasperk C, Wergedal J, Strong D, Farley J, Wangerin K, Gropp H, Ziegler R, Baylink DJ (1995) Human bone cell phenotypes differ depending on their skeletal site of origin. J Clin Endocrinol Metab 80:2511–2517PubMed Kasperk C, Wergedal J, Strong D, Farley J, Wangerin K, Gropp H, Ziegler R, Baylink DJ (1995) Human bone cell phenotypes differ depending on their skeletal site of origin. J Clin Endocrinol Metab 80:2511–2517PubMed
25.
go back to reference Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG (2006) Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38:758–768CrossRefPubMed Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG (2006) Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38:758–768CrossRefPubMed
26.
go back to reference Cheng SL, Zhang SF, Avioli LV (1996) Expression of bone matrix proteins during dexamethasone-induced mineralization of human bone marrow stromal cells. J Cell Biochem 61:182–193CrossRefPubMed Cheng SL, Zhang SF, Avioli LV (1996) Expression of bone matrix proteins during dexamethasone-induced mineralization of human bone marrow stromal cells. J Cell Biochem 61:182–193CrossRefPubMed
27.
go back to reference Eijken M, Koedam M, van Driel M, Buurman CJ, Pols HA, van Leeuwen JP (2006) The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol Cell Endocrinol 248:87–93CrossRefPubMed Eijken M, Koedam M, van Driel M, Buurman CJ, Pols HA, van Leeuwen JP (2006) The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol Cell Endocrinol 248:87–93CrossRefPubMed
28.
go back to reference Lee E, Fertig EJ, Jin K, Sukumar S, Pandey NB, Popel AS (2014) Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nat Commun 5:4715CrossRefPubMed Lee E, Fertig EJ, Jin K, Sukumar S, Pandey NB, Popel AS (2014) Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nat Commun 5:4715CrossRefPubMed
29.
go back to reference Hakimzadeh N, Stewart DJ, Courtman DW (2010) The role of transglutaminase 2 and osteopontin in matrix protein supplemented microencapsulation of marrow stromal cells. Biomaterials 31:9256–9265CrossRefPubMed Hakimzadeh N, Stewart DJ, Courtman DW (2010) The role of transglutaminase 2 and osteopontin in matrix protein supplemented microencapsulation of marrow stromal cells. Biomaterials 31:9256–9265CrossRefPubMed
30.
go back to reference Tang X, Li J, Yu B, Su L, Yu Y, Yan M, Liu B, Zhu Z (2013) Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer. Int J Biol Sci 9:55–66CrossRefPubMed Tang X, Li J, Yu B, Su L, Yu Y, Yan M, Liu B, Zhu Z (2013) Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer. Int J Biol Sci 9:55–66CrossRefPubMed
31.
go back to reference Khodavirdi AC, Song Z, Yang S, Zhong C, Wang S, Wu H, Pritchard C, Nelson PS, Roy-Burman P (2006) Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res 66:883–888CrossRefPubMed Khodavirdi AC, Song Z, Yang S, Zhong C, Wang S, Wu H, Pritchard C, Nelson PS, Roy-Burman P (2006) Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res 66:883–888CrossRefPubMed
32.
go back to reference Yan W, Qian C, Zhao P, Zhang J, Shi L, Qian J, Liu N, Fu Z, Kang C, Pu P, You Y (2010) Expression pattern of osteopontin splice variants and its functions on cell apoptosis and invasion in glioma cells. Neuro Oncol 12:765–775CrossRefPubMedPubMedCentral Yan W, Qian C, Zhao P, Zhang J, Shi L, Qian J, Liu N, Fu Z, Kang C, Pu P, You Y (2010) Expression pattern of osteopontin splice variants and its functions on cell apoptosis and invasion in glioma cells. Neuro Oncol 12:765–775CrossRefPubMedPubMedCentral
33.
go back to reference Takafuji V, Forgues M, Unsworth E, Goldsmith P, Wang XW (2007) An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene 26:6361–6371CrossRefPubMed Takafuji V, Forgues M, Unsworth E, Goldsmith P, Wang XW (2007) An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene 26:6361–6371CrossRefPubMed
34.
go back to reference Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322CrossRefPubMed Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322CrossRefPubMed
35.
go back to reference Chang IC, Chiang TI, Yeh KT, Lee H, Cheng YW (2010) Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporos Int 21:1401–1409CrossRefPubMed Chang IC, Chiang TI, Yeh KT, Lee H, Cheng YW (2010) Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporos Int 21:1401–1409CrossRefPubMed
36.
go back to reference Nishimichi N, Hayashita-Kinoh H, Chen C, Matsuda H, Sheppard D, Yokosaki Y (2011) Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrin alpha9beta1. J Biol Chem 286:11170–11178CrossRefPubMedPubMedCentral Nishimichi N, Hayashita-Kinoh H, Chen C, Matsuda H, Sheppard D, Yokosaki Y (2011) Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrin alpha9beta1. J Biol Chem 286:11170–11178CrossRefPubMedPubMedCentral
37.
go back to reference Nishimichi N, Higashikawa F, Kinoh HH, Tateishi Y, Matsuda H, Yokosaki Y (2009) Polymeric osteopontin employs integrin alpha9beta1 as a receptor and attracts neutrophils by presenting a de novo binding site. J Biol Chem 284:14769–14776CrossRefPubMedPubMedCentral Nishimichi N, Higashikawa F, Kinoh HH, Tateishi Y, Matsuda H, Yokosaki Y (2009) Polymeric osteopontin employs integrin alpha9beta1 as a receptor and attracts neutrophils by presenting a de novo binding site. J Biol Chem 284:14769–14776CrossRefPubMedPubMedCentral
38.
go back to reference Christensen B, Zachariae ED, Scavenius C, Thybo M, Callesen MM, Kloverpris S, Oxvig C, Enghild JJ, Sorensen ES (2014) Identification of transglutaminase reactive residues in human osteopontin and their role in polymerization. PLoS ONE 9:e113650CrossRefPubMedPubMedCentral Christensen B, Zachariae ED, Scavenius C, Thybo M, Callesen MM, Kloverpris S, Oxvig C, Enghild JJ, Sorensen ES (2014) Identification of transglutaminase reactive residues in human osteopontin and their role in polymerization. PLoS ONE 9:e113650CrossRefPubMedPubMedCentral
39.
go back to reference Bandopadhyay M, Bulbule A, Butti R, Chakraborty G, Ghorpade P et al (2014) Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets 18:883–895CrossRefPubMed Bandopadhyay M, Bulbule A, Butti R, Chakraborty G, Ghorpade P et al (2014) Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets 18:883–895CrossRefPubMed
40.
go back to reference O’Loughlin A, Kulkarni M, Vaughan EE, Creane M, Liew A, Dockery P, Pandit A, O’Brien T (2013) Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model. Stem Cell Res Ther 4:158CrossRefPubMedPubMedCentral O’Loughlin A, Kulkarni M, Vaughan EE, Creane M, Liew A, Dockery P, Pandit A, O’Brien T (2013) Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model. Stem Cell Res Ther 4:158CrossRefPubMedPubMedCentral
41.
go back to reference Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100:782–794CrossRefPubMed Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100:782–794CrossRefPubMed
42.
go back to reference Takahashi F, Akutagawa S, Fukumoto H, Tsukiyama S, Ohe Y, Takahashi K, Fukuchi Y, Saijo N, Nishio K (2002) Osteopontin induces angiogenesis of murine neuroblastoma cells in mice. Int J Cancer 98:707–712CrossRefPubMed Takahashi F, Akutagawa S, Fukumoto H, Tsukiyama S, Ohe Y, Takahashi K, Fukuchi Y, Saijo N, Nishio K (2002) Osteopontin induces angiogenesis of murine neuroblastoma cells in mice. Int J Cancer 98:707–712CrossRefPubMed
43.
go back to reference Higashikawa F, Eboshida A, Yokosaki Y (2007) Enhanced biological activity of polymeric osteopontin. FEBS Lett 581:2697–2701CrossRefPubMed Higashikawa F, Eboshida A, Yokosaki Y (2007) Enhanced biological activity of polymeric osteopontin. FEBS Lett 581:2697–2701CrossRefPubMed
44.
go back to reference Zhang Z, Song Y, Zhang X, Tang J, Chen J, Chen Y (2003) Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1. Mech Dev 120:1469–1479CrossRefPubMed Zhang Z, Song Y, Zhang X, Tang J, Chen J, Chen Y (2003) Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1. Mech Dev 120:1469–1479CrossRefPubMed
Metadata
Title
Differential osteopontin expression in human osteoblasts derived from iliac crest and alveolar bone and its role in early stages of angiogenesis
Authors
Martin Wein
Diana Huelter-Hassler
Katja Nelson
Tobias Fretwurst
Susanne Nahles
Guenter Finkenzeller
Brigitte Altmann
Thorsten Steinberg
Publication date
01-01-2019
Publisher
Springer Japan
Published in
Journal of Bone and Mineral Metabolism / Issue 1/2019
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-017-0900-1

Other articles of this Issue 1/2019

Journal of Bone and Mineral Metabolism 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine