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Human osteoarthritic knee cartilage: fingerprinting of adhesion/growth-regulatory galectins in vitro and in situ indicates differential upregulation in severe degeneration

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Abstract

The apparent connection of galectin-3 to chondrocyte survival and osteoarthritis-like cartilage modifications in animal models provided incentive for the mapping of seven members of this family of adhesion/growth-regulatory proteins in human cartilage specimens. Starting with work in vitro, RT-qPCR analyses and immunocytochemistry revealed gene transcription and protein presence in cultured OA chondrocytes, especially for galectin-1, galectin-3 and galectin-8. Immunohistochemistry in clinical specimens with mild and severe cartilage degeneration detected galectins in chondrocytes—with upregulation, especially of galectin-1 in areas of severe degeneration—accompanied by α2,6-sialylation in the pericellular matrix. Given the possibility for additive/antagonistic activities between galectins, these results direct further research toward examining cellular effects of (1) these proteins (alone or in combination) on chondrocytes and (2) remodeling of the chondrocyte glycophenotype.

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References

  • Amano M, Eriksson H, Manning JC, Detjen KM, André S, Nishimura SI, Lehtiö J, Gabius HJ (2012) Tumour suppressor p16INK4a: anoikis-favouring decrease in N/O-glycan/cell surface sialylation by down-regulation of enzymes in sialic acid biosynthesis in tandem in a pancreatic carcinoma model. FEBS J 279:4062–4080

    Article  PubMed  CAS  Google Scholar 

  • André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, Wiedenmann B, von Doeberitz Knebel M, Gress TM, Nishimura SI, Rosewicz S, Gabius HJ (2007) Tumor suppressor p16INK4a: modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells. FEBS J 274:3233–3256

    Article  PubMed  Google Scholar 

  • André S, Singh T, Lacal JC, Smetana K Jr, Gabius HJ (2014) Rho GTPase Rac1: molecular switch within the galectin network and for N-glycan α2,6-sialylation/O-glycan core 1 sialylation in colon cancer in vitro. Folia Biol (Praha) 60:95–107

    Google Scholar 

  • Barondes SH (1997) Galectins: a personal overview. Trends Glycosci Glycotechnol 9:1–7

    Article  CAS  Google Scholar 

  • Boeuf S, Bovée JV, Lehner B, Hogendoorn PC, Richter W (2010) Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours. Histopathology 56:641–651

    Article  PubMed  Google Scholar 

  • Boileau C, Poirier F, Pelletier JP, Guévremont M, Duval N, Martel-Pelletier J, Reboul P (2008) Intracellular localisation of galectin-3 has a protective role in chondrocyte survival. Ann Rheum Dis 67:175–181

    Article  PubMed  CAS  Google Scholar 

  • Bustin SA, Beaulieu JF, Huggett J, Jaggi R, Kibenge FS, Olsvik PA, Penning LC, Toegel S (2010) MIQE précis: practical implementation of minimum standard guidelines for fluorescence-based quantitative real-time PCR experiments. BMC Mol Biol 11:74

    Article  PubMed  PubMed Central  Google Scholar 

  • Carlsson S, Oberg CT, Carlsson MC, Sundin A, Nilsson UJ, Smith D, Cummings RD, Almkvist J, Karlsson A, Leffler H (2007) Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface. Glycobiology 17:663–676

    Article  PubMed  CAS  Google Scholar 

  • Colnot C, Sidhu SS, Poirier F, Balmain N (1999) Cellular and subcellular distribution of galectin-3 in the epiphyseal cartilage and bone of fetal and neonatal mice. Cell Mol Biol 45:1191–1202

    PubMed  CAS  Google Scholar 

  • Colnot C, Sidhu SS, Balmain N, Poirier F (2001) Uncoupling of chondrocyte death and vascular invasion in mouse galectin-3 null mutant bones. Dev Biol 229:203–214

    Article  PubMed  CAS  Google Scholar 

  • Dawson H, André S, Karamitopoulou E, Zlobec I, Gabius HJ (2013) The growing galectin network in colon cancer and clinical relevance of cytoplasmic galectin-3 reactivity. Anticancer Res 33:3053–3059

    PubMed  CAS  Google Scholar 

  • Filer A, Bik M, Parsonage GN, Fitton J, Trebilcock E, Howlett K, Cook M, Raza K, Simmons DL, Thomas AMC, Salmon M, Scheel-Toellner D, Lord JM, Rabinovich GA, Buckley CD (2009) Galectin-3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathways. Arthritis Rheum 60:1604–1614

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Forsman H, Islander U, Andréasson E, Andersson A, Onnheim K, Karlström A, Sävman K, Magnusson M, Brown KL, Karlsson A (2011) Galectin-3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis Rheum 63:445–454

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ, Kayser K (2014) Introduction to glycopathology: the concept, the tools and the perspectives. Diagn Pathol 9:4

    Article  PubMed  PubMed Central  Google Scholar 

  • Gabius HJ, Vehmeyer K (1988) Effect of microenvironment and cell-line type on carbohydrate-binding proteins of macrophage-like cells. Biochem Cell Biol 66:1169–1176

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ, André S, Jiménez-Barbero J, Romero A, Solís D (2011) From lectin structure to functional glycomics: principles of the sugar code. Trends Biochem Sci 36:298–313

    Article  PubMed  CAS  Google Scholar 

  • Gebert J, Kloor M, Lee J, Lohr M, André S, Wagner R, Kopitz J, Gabius HJ (2012) Colonic carcinogenesis along different genetic routes: glycophenotyping of tumor cases separated by microsatellite instability/stability. Histochem Cell Biol 138:339–350

    Article  PubMed  CAS  Google Scholar 

  • Guévremont M, Martel-Pelletier J, Boileau C, Liu FT, Richard M, Fernandes JC, Pelletier JP, Reboul P (2004) Galectin-3 surface expression on human adult chondrocytes: a potential substrate for collagenase-3. Ann Rheum Dis 63:636–643

    Article  PubMed  PubMed Central  Google Scholar 

  • Habermann FA, André S, Kaltner H, Kübler D, Sinowatz F, Gabius HJ (2011) Galectins as tools for glycan mapping in histology: comparison of their binding profiles to the bovine zona pellucida by confocal laser scanning microscopy. Histochem Cell Biol 135:539–552

    Article  PubMed  CAS  Google Scholar 

  • He J, Baum LG (2004) Presentation of galectin-1 by extracellular matrix triggers T cell death. J Biol Chem 279:4705–4712

    Article  PubMed  CAS  Google Scholar 

  • Ideo H, Seko A, Ishizuka I, Yamashita K (2003) The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity. Glycobiology 13:713–723

    Article  PubMed  CAS  Google Scholar 

  • Janelle-Montcalm A, Boileau C, Poirier F, Pelletier JP, Guévremont M, Duval N, Martel-Pelletier J, Reboul P (2007) Extracellular localization of galectin-3 has a deleterious role in joint tissues. Arthritis Res Ther 9:R20

    Article  PubMed  PubMed Central  Google Scholar 

  • Kadirvelraj R, Grant OC, Goldstein IJ, Winter HC, Tateno H, Fadda E, Woods RJ (2011) Structure and binding analysis of Polyporus squamosus lectin in complex with the Neu5Acα 2-6Galβ1-4GlcNAc human-type influenza receptor. Glycobiology 21:973–984

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kaltner H, Gabius HJ (2012) A toolbox of lectins for translating the sugar code: the galectin network in phylogenesis and tumors. Histol Histopathol 27:397–416

    PubMed  CAS  Google Scholar 

  • Kaltner H, Seyrek K, Heck A, Sinowatz F, Gabius H-J (2002) Galectin-1 and galectin-3 in fetal development of bovine respiratory and digestive tracts. Comparison of cell type-specific expression profiles and subcellular localization. Cell Tissue Res 307:35–46

    Article  PubMed  CAS  Google Scholar 

  • Kayser K, Gabius HJ (1997) Graph theory and the entropy concept in histochemistry. Progr Histochem Cytochem 32(2):1–106

    CAS  Google Scholar 

  • Kayser K, Hoeft D, Hufnagl P, Caselitz J, Zick Y, André S, Kaltner H, Gabius H-J (2003) Combined analysis of tumor growth pattern and expression of endogenous lectins as a prognostic tool in primary testicular cancer and its lung metastases. Histol Histopathol 18:771–779

    PubMed  CAS  Google Scholar 

  • Knibbs RN, Goldstein IJ, Ratcliffe RM, Shibuya N (1991) Characterization of the carbohydrate binding specificity of the leukoagglutinating lectin from Maackia amurensis. Comparison with other sialic acid-specific lectins. J Biol Chem 266:83–88

    PubMed  CAS  Google Scholar 

  • Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius HJ (2001) Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem 276:35917–35923

    Article  PubMed  CAS  Google Scholar 

  • Kopitz J, Fik Z, André S, Smetana K Jr, Gabius HJ (2013) Single-site mutational engineering and following monoPEGylation of the human lectin galectin-2: effects on ligand binding, functional aspects, and clearance from serum. Mol Pharm 10:2054–2061

    Article  PubMed  CAS  Google Scholar 

  • Krzeminski M, Singh T, André S, Lensch M, Wu AM, Bonvin AMJJ, Gabius HJ (2011) Human galectin-3 (Mac-2 antigen): defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region. Biochim Biophys Acta 1810:150–161

    Article  PubMed  CAS  Google Scholar 

  • Li S, Yu Y, Koehn CD, Zhang Z, Su K (2013) Galectins in the pathogenesis of rheumatoid arthritis. J Clin Cell Immunol 4:164

    Google Scholar 

  • Liu FT, Yang RY, Hsu DK (2012) Galectins in acute and chronic inflammation. Ann N Y Acad Sci 1253:80–91

    Article  PubMed  CAS  Google Scholar 

  • Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537

    PubMed  CAS  Google Scholar 

  • Marcon P, Marsich E, Vetere A, Mozetic P, Campa C, Donati I, Vittur F, Gamini A, Paoletti S (2005) The role of galectin-1 in the interaction between chondrocytes and a lactose-modified chitosan. Biomaterials 26:4975–4984

    Article  PubMed  CAS  Google Scholar 

  • Marsich E, Mozetic P, Ortolani F, Contin M, Marchini M, Vetere A, Pacor S, Semeraro S, Vittur F, Paoletti S (2008) Galectin-1 in cartilage: expression, influence on chondrocyte growth and interaction with ECM components. Matrix Biol 27:513–525

    Article  PubMed  CAS  Google Scholar 

  • Matsuhashi T, Iwasaki N, Nakagawa H, Hato M, Kurogochi M, Majima T, Minami A, Nishimura SI (2008) Alteration of N-glycans related to articular cartilage deterioration after anterior cruciate ligament transection in rabbits. Osteoarthr Cartil 16:772–778

    Article  PubMed  CAS  Google Scholar 

  • Ohshima S, Kuchen S, Seemayer CA, Kyburz D, Hirt A, Klinzing S, Michel BA, Gay RE, Liu FT, Gay S, Neidhart M (2003) Galectin-3 and its binding protein in rheumatoid arthritis. Arthritis Rheum 48:2788–2795

    Article  PubMed  CAS  Google Scholar 

  • Pabst M, Wu SQ, Grass J, Kolb A, Chiari C, Viernstein H, Unger FM, Altmann F, Toegel S (2010) IL-1β and TNF-α alter the glycophenotype of primary human chondrocytes in vitro. Carbohydr Res 345:1389–1393

    Article  PubMed  CAS  Google Scholar 

  • Ranstam J (2012) Repeated measurements, bilateral observations and pseudoreplicates, why does it matter? Osteoarthr Cartil 20:473–475

    Article  PubMed  CAS  Google Scholar 

  • Reboul P, Martel-Pelletier J, Pelletier JP (2004) Galectin-3 in osteoarthritis: when the fountain of youth doesn’t deliver its promises. Curr Opin Rheumatol 16:595–598

    Article  PubMed  Google Scholar 

  • Roth J (2011) Lectins for histochemical demonstration of glycans. Histochem Cell Biol 136:117–130

    Article  PubMed  CAS  Google Scholar 

  • Ruiz FM, Scholz BA, Buzamet E, Kopitz J, André S, Menéndez M, Romero A, Solís D, Gabius HJ (2014) Natural single amino-acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells. FEBS J 281:1446–1464

    Article  PubMed  CAS  Google Scholar 

  • Saal I, Nagy N, Lensch M, Lohr M, Manning JC, Decaestecker C, André S, Kiss R, Salmon I, Gabius HJ (2005) Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization. Histol Histopathol 20:1191–1208

    PubMed  CAS  Google Scholar 

  • Sanchez-Ruderisch H, Fischer C, Detjen KM, Welzel M, Wimmel A, Manning JC, André S, Gabius HJ (2010) Tumor suppressor p16 INK4a: downregulation of galectin-3, an endogenous competitor of the pro-anoikis effector galectin-1, in a pancreatic carcinoma model. FEBS J 277:3552–3563

    Article  PubMed  CAS  Google Scholar 

  • Sarter K, Janko C, André S, Muñoz LE, Schorn C, Winkler S, Rech J, Kaltner H, Lorenz HM, Schiller M, Andreoli L, Manfredi AA, Isenberg DA, Schett G, Herrmann M, Gabius HJ (2013) Autoantibodies against galectins are associated with antiphospholipid syndrome in patients with systemic lupus erythematosus. Glycobiology 23:12–22

    Article  PubMed  CAS  Google Scholar 

  • Schlötzer-Schrehardt U, André S, Janko C, Kaltner H, Kopitz J, Gabius HJ, Herrmann M (2012) Adhesion/growth-regulatory galectins in the human eye: localization profiles and tissue reactivities as a standard to detect disease-associated alterations. Graefes Arch Clin Exp Ophthalmol 250:1169–1180

    Article  PubMed  Google Scholar 

  • Smetana K Jr, André S, Kaltner H, Kopitz J, Gabius HJ (2013) Context-dependent multifunctionality of galectin-1: a challenge for defining the lectin as therapeutic target. Expert Opin Ther Targets 17:379–392

    Article  PubMed  CAS  Google Scholar 

  • Solís D, Bovin NV, Davis AP, Jiménez-Barbero J, Romero A, Roy R, Smetana K Jr, Gabius HJ (2014) A guide into glycosciences: how chemistry, biochemistry and biology cooperate to crack the sugar code. Biochim Biophys Acta (in press)

  • Stowell SR, Arthur CM, Slanina KA, Horton JR, Smith DF, Cummings RD (2008) Dimeric galectin-8 induces phosphatidylserine exposure in leukocytes through polylactosamine recognition by the C-terminal domain. J Biol Chem 283:20547–20559

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Toegel S, Pabst M, Wu SQ, Grass J, Goldring MB, Chiari C, Kolb A, Altmann F, Viernstein H, Unger FM (2010) Phenotype-related differential α2,6- or α2,3-sialylation of glycoprotein N-glycans in human chondrocytes. Osteoarthr Cartil 18:240–248

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Toegel S, Bieder S, André S, Altmann F, Walzer SM, Kaltner H, Hofstaetter JG, Windhager R, Gabius HJ (2013) Glycophenotyping of osteoarthritic cartilage and chondrocytes by RT-qPCR, mass spectrometry, histochemistry with plant/human lectins and lectin localization with a glyocprotein. Arthritis Res Ther 15:R147

    Article  PubMed  PubMed Central  Google Scholar 

  • Toma V, Zuber C, Winter HC, Goldstein IJ, Roth J (2001) Application of a lectin from the mushroom Polysporus squamosus for the histochemical detection of the NeuAcα2,6Galβ1,4Glc/GlcNAc sequence of N-linked oligosaccharides: a comparison with the Sambucus nigra lectin. Histochem Cell Biol 116:183–193

    PubMed  CAS  Google Scholar 

  • Tsai CM, Guan CH, Hsieh HW, Hsu TL, Tu Z, Wu KJ, Lin CH, Lin KI (2011) Galectin-1 and galectin-8 have redundant roles in promoting plasma cell formation. J Immunol 187:1643–1652

    Article  PubMed  CAS  Google Scholar 

  • Vasta GR, Ahmed H, Nita-Lazar M, Banerjee A, Pasek M, Shridhar S, Guha P, Fernández-Robledo JA (2012) Galectins as self/non-self recognition receptors in innate and adaptive immunity: an unresolved paradox. Front Immunol 3:199

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu G, Lu ZH, Gabius HJ, Ledeen RW, Bleich D (2011) Ganglioside GM1 deficiency in effector T cells from NOD mice induces resistance to regulatory T cell suppression. Diabetes 60:2341–2349

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang B, Palcic MM, Mo H, Goldstein IJ, Hindsgaul O (2001) Rapid determination of the binding affinity and specificity of the mushroom Polyporus squamosus lectin using frontal affinity chromatography coupled to electrospray mass spectrometry. Glycobiology 11:141–147

    Article  PubMed  Google Scholar 

  • Zuber C, Roth J (2009) N-Glycosylation. In: Gabius HJ (ed) The Sugar Code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 87–110

    Google Scholar 

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Acknowledgments

This work was generously supported by EC funding (Grant agreements 260600 (GlycoHIT) and 317297 (GLYCOPHARM)) and the Verein zur Förderung des biologisch-technologischen Fortschritts in der Medizin e. V. (Heidelberg, Germany). Insightful discussions with Dr. J. Domingo-Ekark and Dr. B. Friday are gratefully acknowledged, as is the valuable input of the reviewers. Ruth Grübl-Barabas, Bettina Rodriguez-Molina and Melanie Cezanne are acknowledged for excellent technical assistance.

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Correspondence to Stefan Toegel or Hans-Joachim Gabius.

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Toegel, S., Bieder, D., André, S. et al. Human osteoarthritic knee cartilage: fingerprinting of adhesion/growth-regulatory galectins in vitro and in situ indicates differential upregulation in severe degeneration. Histochem Cell Biol 142, 373–388 (2014). https://doi.org/10.1007/s00418-014-1234-x

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