Pyrroloquinoline quinone promotes chondrocyte proliferation and inhibits interleukin-1beta-induced chondrocyte apoptosis

doi:10.3969/j.issn.2095-4344.2015.15.002

Abstract

Abstract:

BACKGROUND: Pyrroloquinoline quinone is found to accelerate Schwann cell proliferation and growth factor secretion, but there is no report addressing its role in articular cartilage and chondrocytes.
OBJECTIVE: To investigate the role of pyrroloquinoline quinone in chondrocyte proliferation and interleukin-1β-induced chondrocyte apoptosis in the articular cartilage of knee joints and to verify the protective mechanism involved.
METHODS: Chondrocytes were isolated from New Zealand white rabbits (1 month of age), digested under aseptic conditions, and cultured in DMEM/F12 in the presence of 10% fetal bovine serum to allow for proliferation until passage 2. Adherent chondrocytes were cultured in serum-free DMEM/F12 medium with 0, 6.25, 12.5, 25.0, 50.0 and 100.0 μmol/L pyrroloquinoline quinone, separately. Proliferation activity was determined by MTT at 48 hours of pyrroloquinoline quinone administration. Cell cycle was determined by flow cytometry at 30 hours after pyrroloquinoline quinone administration. Apoptosis was determined by flow cytometry following 24 hours of pyrroloquinoline quinone pretreatment and 15 hours of interleukin-1β induction.
RESULTS AND CONCLUSION: Pyrroloquinoline quinone enhanced chondrocyte proliferation activity, increased percentage of S phase and G2/M phase in a dose dependent manner and reached the peak when the concentration of pyrroloquinoline quinone was 12.5-25.0 μmol/L (P < 0.05). Pyrroloquinoline quinone also inhibited interleukin-1β-induced chondrocyte apoptosis in early and late stage, and 25.0 μmol/L pyrroloquinoline quinone had the best effects (P < 0.05). These findings suggest pyrroloquinoline quinone can promote chondrocyte division and proliferation, and protect the cells from interleukin-1β-induced apoptosis.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: Chondrocytes, Interleukin-1beta, Apoptosis

CLC Number:

R318

Zhang Zhen-jiang, Lv Guo-feng. Pyrroloquinoline quinone promotes chondrocyte proliferation and inhibits interleukin-1beta-induced chondrocyte apoptosis[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(15): 2305-2309.

Figures/Tables 4

References

[1] KIm HA, Blanco FJ.Cell death and apoptpsis in osteoarthrifis cartilage. Current Drug Targets. 2007;8(2):333-345.
[2] Kasahara T, Kat o T .Nutritional biochemistry:A new redox-cofactor vitamin for mammals.Nature. 2003;422( 6934): 832.
[3] Steinberg F,Stites TE, Anderson P,et al.Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets[J]. Exp Biol Med.2003; 228:160-166 .
[4] Andrea C R, Antonio R, Augusto R,et al. Modeling novel quinocofactors: An overview.Bioorganic Chemistry. 1999; 27(4): 253-288.
[5] Heurteaux C, Gandin C, Borsotto M.et al. Neuroprotective and neuroproliferative activities of NeuroAid (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology.2010;58:987-1001.
[6] He K, Nukada H, Urakami T,et al. Antioxidant and pro-oxidant properties of pyrroloquinoline quinone(PQQ): implications for its function in biological systems. Biochemical Pharmacology. 2003;65 (1):67-74.
[7] 熊顺华,王君,龚坚,等.吡咯喹啉醌对培养的鼠海马神经元的促生长作用[J].陕西医学杂志,2007,35(5):527-572.
[8] Zhang Q, Shen M, Ding M, et al.The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K Akt pathway.Toxicology and Applied Pharmacology.2001;252(1):62-72.
[9] 贺斌,刘世淸,李浩恒.PI3K/Akt信号通路在吡咯喹啉醌促雪旺细胞增殖中的作用[J].中华整形外科杂志,2010,26(1):53-56.
[10] Rochard P, Rodier A, Casas F,et al. Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors.J Biol Chem.2000;275(4):2733-2744.
[11] Schauen M, Spitkovsky D, Schubert J,et al. Respiratory chain deficiency slows down cell-cycle progression via reduced ROS generation and is associated with a reduction of p21CIP1/WAF1.J Cell Physiol.2006;209(1):103-112.
[12] Stites T, Storms D, Bauerly K,et al.Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice.J Nutr. 2006;136(2):390-396.
[13] Naito Y,Kumazawa T, Kino I, et al .Effects of pyrroloquinoline quinone(PQQ)and PQQ-oxazole on DNA synthesis of cultured human fibroblasts.Life Sci.1993; 52(24):1909-1915.
[14] Rajpurohit YS，Gopalakrishnan R，Misra HS．Involvement of a protein kinase activity inducer in DNA double strand break repair and radioresistance of Deinococcus radiodurans. J Bacteriol.2008;190(11):3948-3954．
[15] Khaimar NP, Kamble VA, Mangoli SH, et al. Involvement of a periplasmie protein kinase in DNA strand break repair and homologous recombination in Escherichia coli. Mol Microbiol. 2007;65(2):294-304．
[16] Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Binphys Res Commun. 2007;363(2):257-262．
[17] Misra HS, Khairnar NP,Barik A,et al.Pyrroloquinoline quinone a reactive oxygen species scavenger in bacteria.FEBS Lett. 2004;578(1-2):26-30.
[18] Zhu BQ, Simonis U, Cecchini G, et al. Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury.J Cardiovasc Pharmacol Ther. 2006;11(2):119-128.
[19] Zhang Y, Feustel PJ,Kimelberg HK.Neuroprotection by pyrroloquinoline quinone(PQQ)in reversible middle cerebral artery occlusion in the adult rat.Brain Res. 2006;1094(1): 200-206.
[20] Zhang JJ, Zhang RF,Meng XK.Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.Neurosci Lett. 2009; 464(3):165-169.