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Published in: Knee Surgery, Sports Traumatology, Arthroscopy 11/2012

01-11-2012 | Experimental Study

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro

Authors: Xiaozhou Ying, Wei Zhang, Shaowen Cheng, Pengfei Nie, Xiaojie Cheng, Yue Shen, Wei Wang, Enxing Xue, Qingyu Chen, Dongquan Kou, Lei Peng, Yu Zhang, Chuanzhu Lu

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 11/2012

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Abstract

Purpose

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10−7, 10−6 and 10−5 M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro.

Methods

BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue.

Results

The cell viability was not significantly impaired until up to a concentration of 10−5 M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10−6 M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10−5 M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10−7 and 10−6 M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10−7–10−5 M nicotine (P < 0.05).

Conclusion

It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.
Literature
1.
go back to reference Abdallah BM, Kassem M (2009) The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives. J Cell Physiol 218(1):9–12PubMedCrossRef Abdallah BM, Kassem M (2009) The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives. J Cell Physiol 218(1):9–12PubMedCrossRef
2.
go back to reference Borenfreund E, Puerner JA (1985) Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24(2–3):119–124PubMedCrossRef Borenfreund E, Puerner JA (1985) Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24(2–3):119–124PubMedCrossRef
3.
go back to reference Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895PubMedCrossRef Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895PubMedCrossRef
4.
go back to reference Fang MA, Frost PJ, Iida-Klein A, Hahn TJ (1991) Effects of nicotine on cellular function in UMR 106–01 osteoblast-like cells. Bone 12(4):283–286PubMedCrossRef Fang MA, Frost PJ, Iida-Klein A, Hahn TJ (1991) Effects of nicotine on cellular function in UMR 106–01 osteoblast-like cells. Bone 12(4):283–286PubMedCrossRef
5.
go back to reference Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883(2):173–177PubMedCrossRef Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883(2):173–177PubMedCrossRef
6.
go back to reference Fogelholm RR, Alho AV (2001) Smoking and intervertebral disc degeneration. Med Hypotheses 56(4):537–539PubMedCrossRef Fogelholm RR, Alho AV (2001) Smoking and intervertebral disc degeneration. Med Hypotheses 56(4):537–539PubMedCrossRef
7.
go back to reference Fujii T, Takada-Takatori Y, Kawashima K (2008) Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J Pharmacol Sci 106(2):186–192PubMedCrossRef Fujii T, Takada-Takatori Y, Kawashima K (2008) Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J Pharmacol Sci 106(2):186–192PubMedCrossRef
8.
go back to reference Gullahorn L, Lippiello L, Karpman R (2005) Smoking and osteoarthritis: differential effect of nicotine on human chondrocyte glycosaminoglycan and collagen synthesis. Osteoarthr Cartil 13(10):942–943PubMedCrossRef Gullahorn L, Lippiello L, Karpman R (2005) Smoking and osteoarthritis: differential effect of nicotine on human chondrocyte glycosaminoglycan and collagen synthesis. Osteoarthr Cartil 13(10):942–943PubMedCrossRef
9.
go back to reference Henrotin Y, Addison S, Kraus V, Deberg M (2007) Type II collagen markers in osteoarthritis: what do they indicate? Curr Opin Rheumatol 19(5):444–450PubMedCrossRef Henrotin Y, Addison S, Kraus V, Deberg M (2007) Type II collagen markers in osteoarthritis: what do they indicate? Curr Opin Rheumatol 19(5):444–450PubMedCrossRef
10.
go back to reference Hoffmann D, Adams JD (1981) Carcinogenic tobacco-specific N-nitrosamines in snuff and in the saliva of snuff dippers. Cancer Res 41(11 Pt 1):4305–4308PubMed Hoffmann D, Adams JD (1981) Carcinogenic tobacco-specific N-nitrosamines in snuff and in the saliva of snuff dippers. Cancer Res 41(11 Pt 1):4305–4308PubMed
11.
go back to reference Hoogduijn MJ, Cheng A, Genever PG (2009) Functional nicotinic and muscarinic receptors on mesenchymal stem cells. Stem Cells Dev 18(1):103–112PubMedCrossRef Hoogduijn MJ, Cheng A, Genever PG (2009) Functional nicotinic and muscarinic receptors on mesenchymal stem cells. Stem Cells Dev 18(1):103–112PubMedCrossRef
12.
go back to reference Hukkanen J, Jacob P 3rd, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57(1):79–115PubMedCrossRef Hukkanen J, Jacob P 3rd, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57(1):79–115PubMedCrossRef
13.
go back to reference Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10(6):432–463PubMedCrossRef Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10(6):432–463PubMedCrossRef
14.
go back to reference Jaiswal PK, Macmull S, Bentley G, Carrington RW, Skinner JA, Briggs TW (2009) Does smoking influence outcome after autologous chondrocyte implantation?A case-controlled study. J Bone Joint Surg Br 91(12):1575–1578PubMedCrossRef Jaiswal PK, Macmull S, Bentley G, Carrington RW, Skinner JA, Briggs TW (2009) Does smoking influence outcome after autologous chondrocyte implantation?A case-controlled study. J Bone Joint Surg Br 91(12):1575–1578PubMedCrossRef
15.
go back to reference Kaila-Kangas L, Leino-Arjas P, Riihimaki H, Luukkonen R, Kirjonen J (2003) Smoking and overweight as predictors of hospitalization for back disorders. Spine 28(16):1860–1868 Kaila-Kangas L, Leino-Arjas P, Riihimaki H, Luukkonen R, Kirjonen J (2003) Smoking and overweight as predictors of hospitalization for back disorders. Spine 28(16):1860–1868
16.
go back to reference Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, Sideri A, Zouridakis M, Tzartos SJ (2007) Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. FEBS J 274(15):3799–3845PubMedCrossRef Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, Sideri A, Zouridakis M, Tzartos SJ (2007) Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. FEBS J 274(15):3799–3845PubMedCrossRef
17.
go back to reference Kawakita A, Sato K, Makino H, Ikegami H, Takayama S, Toyama Y, Umezawa A (2008) Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor. PLoS One 3(12):e3945PubMedCrossRef Kawakita A, Sato K, Makino H, Ikegami H, Takayama S, Toyama Y, Umezawa A (2008) Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor. PLoS One 3(12):e3945PubMedCrossRef
18.
go back to reference Ma L, Sham MH, Zheng LW, Cheung LK (2011) Influence of low-dose nicotine on bone healing. J Trauma 70(6):E117–E121PubMedCrossRef Ma L, Sham MH, Zheng LW, Cheung LK (2011) Influence of low-dose nicotine on bone healing. J Trauma 70(6):E117–E121PubMedCrossRef
19.
go back to reference Mandelbaum BR, Browne JE, Fu F, Micheli L, Mosely JB Jr, Erggelet C, Minas T, Peterson L (1998) Articular cartilage lesions of the knee. Am J Sports Med 26(6):853–861PubMed Mandelbaum BR, Browne JE, Fu F, Micheli L, Mosely JB Jr, Erggelet C, Minas T, Peterson L (1998) Articular cartilage lesions of the knee. Am J Sports Med 26(6):853–861PubMed
20.
go back to reference Meidinger G, Imhoff AB, Paul J, Kirchhoff C, Sauerschnig M, Hinterwimmer S (2011) May smokers and overweight patients be treated with a medial open-wedge HTO? Risk factors for non-union. Knee Surg Sports Traumatol Arthrosc 19(3):333–339PubMedCrossRef Meidinger G, Imhoff AB, Paul J, Kirchhoff C, Sauerschnig M, Hinterwimmer S (2011) May smokers and overweight patients be treated with a medial open-wedge HTO? Risk factors for non-union. Knee Surg Sports Traumatol Arthrosc 19(3):333–339PubMedCrossRef
21.
go back to reference Nelson E, Jodscheit K, Guo Y (1999) Maternal passive smoking during pregnancy and fetal developmental toxicity. Part 1: gross morphological effects. Hum Exp Toxicol 18(4):252–256PubMedCrossRef Nelson E, Jodscheit K, Guo Y (1999) Maternal passive smoking during pregnancy and fetal developmental toxicity. Part 1: gross morphological effects. Hum Exp Toxicol 18(4):252–256PubMedCrossRef
22.
go back to reference Ortega N, Behonick DJ, Werb Z (2004) Matrix remodeling during endochondral ossification. Trends Cell Biol 14(2):86–93PubMedCrossRef Ortega N, Behonick DJ, Werb Z (2004) Matrix remodeling during endochondral ossification. Trends Cell Biol 14(2):86–93PubMedCrossRef
23.
go back to reference Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54(10):3254–3266PubMedCrossRef Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54(10):3254–3266PubMedCrossRef
24.
go back to reference Pereira ML, Carvalho JC, Peres F, Fernandes MH (2009) Effect of nicotine in matrix mineralization by human bone marrow and Saos-2 cells cultured on the surface of plasma-sprayed titanium implants. J Biomed Mater Res A 88(1):84–93PubMed Pereira ML, Carvalho JC, Peres F, Fernandes MH (2009) Effect of nicotine in matrix mineralization by human bone marrow and Saos-2 cells cultured on the surface of plasma-sprayed titanium implants. J Biomed Mater Res A 88(1):84–93PubMed
25.
go back to reference Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R (2009) Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab 27(5):555–561PubMedCrossRef Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R (2009) Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab 27(5):555–561PubMedCrossRef
26.
go back to reference Schraufstatter IU, DiScipio RG, Khaldoyanidi SK (2009) Alpha 7 subunit of nAChR regulates migration of human mesenchymal stem cells. J Stem Cells 4(4):203–215PubMed Schraufstatter IU, DiScipio RG, Khaldoyanidi SK (2009) Alpha 7 subunit of nAChR regulates migration of human mesenchymal stem cells. J Stem Cells 4(4):203–215PubMed
27.
go back to reference Schulze-Tanzil G, de Souza P, Villegas Castrejon H, John T, Merker HJ, Scheid A, Shakibaei M (2002) Redifferentiation of dedifferentiated human chondrocytes in high-density cultures. Cell Tissue Res 308(3):371–379PubMedCrossRef Schulze-Tanzil G, de Souza P, Villegas Castrejon H, John T, Merker HJ, Scheid A, Shakibaei M (2002) Redifferentiation of dedifferentiated human chondrocytes in high-density cultures. Cell Tissue Res 308(3):371–379PubMedCrossRef
28.
go back to reference Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF (2010) Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A 16(3):1009–1019PubMedCrossRef Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF (2010) Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A 16(3):1009–1019PubMedCrossRef
29.
go back to reference Tuan RS, Boland G, Tuli R (2003) Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 5(1):32–45PubMedCrossRef Tuan RS, Boland G, Tuli R (2003) Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 5(1):32–45PubMedCrossRef
30.
go back to reference Valacchi G, Rimbach G, Saliou C, Weber SU, Packer L (2001) Effect of benzoyl peroxide on antioxidant status, NF-kappa B activity and interleukin-1 alpha gene expression in human keratinocytes. Toxicology 165(2–3):225–234PubMedCrossRef Valacchi G, Rimbach G, Saliou C, Weber SU, Packer L (2001) Effect of benzoyl peroxide on antioxidant status, NF-kappa B activity and interleukin-1 alpha gene expression in human keratinocytes. Toxicology 165(2–3):225–234PubMedCrossRef
31.
go back to reference Vasan NS, Lash JW (1979) Monomeric and aggregate proteoglycans in the chondrogenic differentiation of embryonic chick limb buds. J Embryol Exp Morphol 49:47–59PubMed Vasan NS, Lash JW (1979) Monomeric and aggregate proteoglycans in the chondrogenic differentiation of embryonic chick limb buds. J Embryol Exp Morphol 49:47–59PubMed
32.
go back to reference Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76(4):579–592PubMed Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76(4):579–592PubMed
33.
go back to reference Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML (2010) Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials 31(4):631–640PubMedCrossRef Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML (2010) Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials 31(4):631–640PubMedCrossRef
34.
go back to reference Ying X, Cheng S, Shen Y, Cheng X, An Rompis F, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Peng L, Tian XQ, Lu CZ (2012) Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients. Mol Cell Biochem 359(1–2):263–269PubMedCrossRef Ying X, Cheng S, Shen Y, Cheng X, An Rompis F, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Peng L, Tian XQ, Lu CZ (2012) Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients. Mol Cell Biochem 359(1–2):263–269PubMedCrossRef
35.
go back to reference Ying X, Cheng S, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Shen Y, Cheng X, Peng L, Zi Xu H, Zhu Lu C (2011) Effect of lactoferrin on osteogenic differentiation of human adipose stem cells. Int Orthop. doi:10.1007/s00264-011-1303-x PubMed Ying X, Cheng S, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Shen Y, Cheng X, Peng L, Zi Xu H, Zhu Lu C (2011) Effect of lactoferrin on osteogenic differentiation of human adipose stem cells. Int Orthop. doi:10.​1007/​s00264-011-1303-x PubMed
Metadata
Title
Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro
Authors
Xiaozhou Ying
Wei Zhang
Shaowen Cheng
Pengfei Nie
Xiaojie Cheng
Yue Shen
Wei Wang
Enxing Xue
Qingyu Chen
Dongquan Kou
Lei Peng
Yu Zhang
Chuanzhu Lu
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 11/2012
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-012-1890-0

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