[en] Chondroitin sulfate (CS)-calcium complex (CSCa) was fabricated, and the structural characteristics of CSCa and its proliferative bioactivity to the chondrocyte were investigated in vitro. Results suggested calcium ions could bind CS chains forming polysaccharide-metal complex, and the maximum calcium holding capacity of CSCa reached 4.23 %. Characterization of CSCa was performed by EDS, AFM, FTIR, UV, XRD and 1H-NMR. It was found that calcium ions were integrated with CS by binding the sulfate or carboxyl groups. The thermal properties analysis indicated CSCa had a good thermal stability by TGA and DSC. CSCa could interact the calcium-sensing receptor increasing the intracellular calcium ions and influence the cell cycle. The TGF-β1 secretion induced by CSCa could activate the TGF-β/Smads pathway and change the genes associated proliferation expression ultimately leading to the chondrocyte proliferation. This research probably has an important implication for understanding the effect of CSCa on bone care as food supplements.
Zhang, Chunhui; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Electronic address: dr_zch@163.com
Mo, Haizhen; School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, China
Zhang, Hongru ; Université de Liège - ULiège > TERRA Research Centre
Qin, Xiaojie; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Li, Juan; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Zhang, Zhiqiang; Shandong Haiyu Biotechnology Co., Ltd., Jining, 272113, China
Richel, Aurore ; Université de Liège - ULiège > TERRA Research Centre > Smart Technologies for Food and Biobased Products (SMARTECH)
Language :
English
Title :
Fabrication of chondroitin sulfate calcium complex and its chondrocyte proliferation in vitro.
Central Public-interest Scientific Institution Basal Research Fund, Chinese Academy of Fishery Sciences Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences
Funding text :
This work was supported by the grants of “ Central Public-interest Scientific Institution Basal Research Fund ( Y2020PT33 )” and “ Technology Innovation Program ( CAAS-ASTIP-2020-IFST-05 )”.
Balk, S.D., Calcium as a regulator of the proliferation of normal, but not of transformed, chicken fibroblasts in a plasma-containing medium. Proceedings of the National Academy of Sciences 68:2 (1971), 271–275.
Beier, F., Ali, Z., Mok, D., Taylor, A.C., Leask, T., Albanese, C., et al. TGFβ and PTHrP control chondrocyte proliferation by activating cyclin D1 expression. Molecular Biology of the Cell 12:12 (2001), 3852–3863.
Boynton, A.L., Whitfield, J.F., Isaacs, R.J., Tremblay, R.G., Different extracellular calcium requirements for proliferation of nonneoplastic, preneoplastic, and neoplastic mouse cells. Cancer Research 37:8 Pt 1 (1977), 2657–2661.
Brown, E.M., Role of the calcium-sensing receptor in extracellular calcium homeostasis. Best Practice & Research. Clinical Endocrinology & Metabolism 27:3 (2013), 333–343.
Cao, C., Ren, Y., Barnett, A.S., Mirando, A.J., Rouse, D., Mun, S.H., et al. Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss. JCI Insight, 2(22), 2017, e95512.
Capiod, T., The need for calcium channels in cell proliferation. Recent Patent on Anti-cancer Drug Discovery 8:1 (2013), 4–17.
Capiod, T., Extracellular calcium has multiple targets to control cell proliferation. Advances in Experimental Medicine and Biology 898 (2016), 133–156.
Chen, G., Deng, C., Li, Y.P., TGF-β and BMP signaling in osteoblast differentiation and bone formation. International Journal of Biological Sciences 8:2 (2012), 272–288.
Chen, G.Q., Wang, S., Hu, S.Y., Osteoporosis increases chondrocyte proliferation without a change in apoptosis during fracture healing in an ovariectomized rat model. Molecular Medicine Reports 5:1 (2012), 202–206.
Datto, M., Wang, X.F., The Smads: Transcriptional regulation and mouse models. Cytokine Growth & Factor Reviews 11:1–2 (2000), 37–48.
Dong, S., Li, G., Zheng, D., Wu, J., Sun, D., Yang, F., et al. A novel role for the calcium sensing receptor in rat diabetic encephalopathy. Cellular Physiology and Biochemistry 35:1 (2015), 38–50.
Durham, A.C., Walton, J.M., Calcium ions and the control of proliferation in normal and cancer cells. Bioscience Reports 2:1 (1982), 15–30.
Fenbo, M., Xingyu, X., Bin, T., Strontium chondroitin sulfate/silk fibroin blend membrane containing microporous structure modulates macrophage responses for guided bone regeneration. Carbohydrate Polymers 213 (2019), 266–275.
Feng, X.H., Derynck, R., Specificity and versatility in tgf-beta signaling through smads. Annual Review of Cell Developmental Biology 21 (2005), 659–693.
Guo, X., Wang, X.F., Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Research 19:1 (2009), 71–88.
He, W., Fu, L., Li, G., Andrew Jones, J., Linhardt, R.J., Koffas, M., Production of chondroitin in metabolically engineered E. coli. Metabolic Engineering 27 (2015), 92–100.
Hendy, G.N., Canaff, L., Calcium-sensing receptor gene: Regulation of expression. Frontiers in Physiology, 7, 2016, 394.
Henrotin, Y., Marty, M., Mobasheri, A., What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis?. Maturitas 78:3 (2014), 184–187.
Honda, Y., Fitzsimmons, R.J., Baylink, D.J., Mohan, S., Effects of extracellular calcium on insulin-like growth factor II in human bone cells. Journal of Bone Mineral Research 10:11 (1995), 1660–1665.
Huang, F., Liu, H., Zhang, R., Dong, L., Liu, L., Ma, Y., et al. Physicochemical properties and prebiotic activities of polysaccharides from longan pulp based on different extraction techniques. Carbohydrate Polymers 206 (2019), 344–351.
Ichikawa, J., Inoue, R., TRPC6 regulates cell cycle progression by modulating membrane potential in bone marrow stromal cells. British Journal of Pharmacology 171:23 (2014), 5280–5294.
Kaunitz, A.M., Mcclung, M.R., Feldman, R.G., Wysocki, S.J.J.F.P., Postmenopausal osteoporosis: Fracture risk and prevention. The Journal of Family Practice 58:11 Suppl Postmenopausal (2009), 1–6.
Kobayashi, T., Soegiarto, D.W., Yang, Y., Lanske, B., Schipani, E., McMahon, A.P., et al. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. The Jounal of Clinical Investigation 115:7 (2005), 1734–1742.
Komori, T., Cell death in chondrocytes, osteoblasts, and osteocytes. International Journal of Molecular Sciences, 17(12), 2016, 2045.
Komori, T., Runx2, an inducer of osteoblast and chondrocyte differentiation. Histochemistry and Cell Biology 149:4 (2018), 313–323.
Lai, C.F., Cheng, S.L., Signal transductions induced by bone morphogenetic protein-2 and transforming growth factor-beta in normal human osteoblastic cells. The Journal of Biological Chemistry 277:18 (2002), 15514–15522.
Long, F., Zhang, X.M., Karp, S., Yang, Y., McMahon, A.P., Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development 128:24 (2001), 5099–5108.
Loveridge, N., Farquharson, C., Studies on growth plate chondrocytes in situ: Cell proliferation and differentiation. Acta Paediatrica Supplement 82:Suppl 391 (1993), 42–48.
Ma, F.B., Liu, N., Hu, N., Wen, C.Y., Tang, B., Synthesis of strontium chondroitin sulfate and the evaluation of its capability to attenuate osteoarthritis. Carbohydrate Polymers 170 (2017), 217–225.
Machaca, K., Ca2+ signaling, genes and the cell cycle. Cell Calcium 49:5 (2011), 323–330.
Marie, P.J., The calcium-sensing receptor in bone cells: A potential therapeutic target in osteoporosis. Bone 46:3 (2010), 571–576.
Matsunobu, T., Torigoe, K., Ishikawa, M., de Vega, S., Kulkarni, A.B., Iwamoto, Y., et al. Critical roles of the TGF-beta type I receptor ALK5 in perichondrial formation and function, cartilage integrity, and osteoblast differentiation during growth plate development. Developmental Biology 332:2 (2009), 325–338.
Miao, Y., Shen, Q., Zhang, S., Huang, H., Meng, X., Zheng, X., et al. Calcium-sensing stromal interaction molecule 2 upregulates nuclear factor of activated T cells 1 and transforming growth factor-β signaling to promote breast cancer metastasis. Breast Cancer Research, 21(1), 2019, 99.
Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry 30:16 (2009), 2785–2791.
Mou, J., Li, Q., Shi, W., Qi, X., Song, W., Yang, J., Chain conformation, physicochemical properties of fucosylated chondroitin sulfate from sea cucumber Stichopus chloronotus and its in vitro fermentation by human gut microbiota. Carbohydrate Polymers, 228, 2020, 115359.
Mourão, P.A., Pereira, M.S., Pavão, M.S., Mulloy, B., Tollefsen, D.M., Mowinckel, M.C., et al. Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action. The Journal of Biological Chemistry 271:39 (1996), 23973–23984.
Nüchel, J., Ghatak, S., Zuk, A.V., Illerhaus, A., Mörgelin, M., Schönborn, K., et al. TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators. Autophagy 14:3 (2018), 465–486.
Shen, Q., Zhang, C., Jia, W., Qin, X., Cui, Z., Mo, H., et al. Co-production of chondroitin sulfate and peptide from liquefied chicken sternal cartilage by hot-pressure. Carbohydrate Polymers, 222, 2019, 115015.
Sobel, A.E., Burger, M., Calcification. XIV. Investigation of the role of chondroitin sulfate in the calcifying mechanism. Proceeding of the Society for Experimental Biology and Medicine 87:1 (1954), 7–13.
Sugimoto, T., Kanatani, M., Kano, J., Kaji, H., Tsukamoto, T., Yamaguchi, T., et al. Effects of high calcium concentration on the functions and interactions of osteoblastic cells and monocytes and on the formation of osteoclast-like cells. Journal of Bone Mineral Research 8:12 (1993), 1445–1452.
Tat, S.K., Pelletier, J.P., Mineau, F., Duval, N., Martel-Pelletier, J., Variable effects of 3 different chondroitin sulfate compounds on human osteoarthritic cartilage/chondrocytes: Relevance of purity and production process. The Journal of Rheumatology 37:3 (2010), 656–664.
Tharmalingam, S., Hampson, D.R., The calcium-sensing receptor and integrins in cellular differentiation and migration. Frontiers in Physiology, 7, 2016, 190.
Uchisawaa, H., Okuzaki, B., Ichita, J., Matsue, H., Binding between calcium ions and chondroitin sulfate chains of salmon nasal cartilage glycosaminoglycan. International Congress Series, 2001.
Wang, C., Zhang, D., Zhang, M., Jiao, Y., Jiang, K., Yan, C.J., Structural characterization of a novel oligosaccharide from Achyranthes bidentata and its anti-osteoporosis activities. Industrial Crops and Products 108 (2017), 458–469.
Wang, L.F., Shen, S.S., Lu, S.C.J., Synthesis and characterization of chondroitin sulfate–methacrylate hydrogels. Carbohydrate Polymers 52:4 (2003), 389–396.
Weng, X., Lin, P., Liu, F., Chen, J., Li, H., Huang, L., et al. Achyranthes bidentata polysaccharides activate the Wnt/β-catenin signaling pathway to promote chondrocyte proliferation. Internaltional Journal of Molecular Medicine 34:4 (2014), 1045–1050.
Woodward, C., Davidson, E.A., Structure-function relationships of protein polysaccharide complexes: Specific ion-binding properties. Proceedings of the National Academy of Sciences 60:1 (1968), 201–205.
Wu, M., Chen, G., Li, Y.P., TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Research, 4, 2016, 16009.
Wuelling, M., Vortkamp, A., Transcriptional networks controlling chondrocyte proliferation and differentiation during endochondral ossification. Pediatric Nephrology 25:4 (2010), 625–631.
Xie, X., Liu, M., Meng, Q., Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone & Joint Research 8:7 (2019), 323–332.
Yan, C., Zhang, S., Wang, C., Zhang, Q., A fructooligosaccharide from Achyranthes bidentata inhibits osteoporosis by stimulating bone formation. Carbohydrate Polymers 210 (2019), 110–118.
Yoshida, C.A., Yamamoto, H., Fujita, T., Furuichi, T., Ito, K., Inoue, K., et al. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes & Development 18:8 (2004), 952–963.
Yoshida, K.-i., Minami, Y., Nemoto, H., Numata, K., Yamanaka, E., Structure of DHG, a depolymerized glycosaminoglycan from sea cucumber, Stichopus japonicus. Tetrahedron Letters 33:34 (1992), 4959–4962.
Yu, F., Li, X., Cai, L., Li, H., Chen, J., Wong, X., et al. Achyranthes bidentata polysaccharides induce chondrocyte proliferation via the promotion of the G1/S cell cycle transition. Molecular Medicine Reports 7:3 (2013), 935–940.
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B., et al. Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts. Molecular Medicine Reports 20:2 (2019), 1093–1102.
Zhang, C., Zhang, T., Zou, J., Miller, C.L., Gorkhali, R., Yang, J.Y., et al. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Science Advance, 2(5), 2016, e1600241.
Zhang, M., Wang, Y., Zhang, Q., Wang, C., Zhang, D., Wan, J.B., et al. UPLC/Q-TOF-MS-based metabolomics study of the anti-osteoporosis effects of Achyranthes bidentata polysaccharides in ovariectomized rats. International Journal of Biological Macromolecules 112 (2018), 433–441.
Zhang, W.H., Fu, S.B., Lu, F.H., Wu, B., Gong, D.M., Pan, Z.W., et al. Involvement of calcium-sensing receptor in ischemia/reperfusion-induced apoptosis in rat cardiomyocytes. Biochemical and Biophysical Research Communications 347:4 (2006), 872–881.
Zhao, L., Liu, M., Wang, J., Zhai, G., Chondroitin sulfate-based nanocarriers for drug/gene delivery. Carbohydrate Polymers 133 (2015), 391–399.
