Osteogenesis effects and mechanisms of Kidney Chinese Herbs after fractures

doi:10.3969/j.issn.2095-4344.2015.15.028

Abstract

Abstract:

BACKGROUND: Fracture healing is the coupling interaction of osteoblasts and osteoclasts that promotes bone growth, in which osteoblast-mediated bone resorption and osteoclasts-mediated bone reconstruction make the bone reconstruction in a dynamic equilibrium to promote bone growth. However, the majorities of the current studies focus on osteogenic or osteoclastic mechanism alone, and ignore the interaction mechanism between these two cells under co-existing conditions.
OBJECTIVE: To investigate the effects of Kidney Chinese Herbs on osteoblasts and osteoclasts coupling of osteoprotegerin-receptor activator of nuclear factor kappaB ligand-receptor activator of nuclear factor kappaB and its mechanism of action in fracture treatment.
METHODS: Mouse osteoblasts and osteoclasts were isolated and cultured in vitro to establish the mouse “osteoblast-osteoclast co-culture system” as a research platform. Then, Kidney Chinese Herbs at doses of 1.25, 2.5, 6.25 g/(kg•d) were given intragastrically for 7 consecutive days. Mice in the blank control group were fed with the same volume of normal saline.
RESULTS AND CONCLUSION: The alkaline phosphatase activity in osteoblasts co-cultured with osteoclasts was significantly higher than that in osteoblasts cultured alone at 24 hours of culture (P < 0.05). Real-time PCR showed that in the co-culture system, the expression of alkaline phosphatase, Runt related transcription factor 2 and osteoprotegerin were increased in a dose-dependent manner (P < 0.05). Western blot assay showed 6.25 g/(kg•d) Kidney Chinese Herbs could dramatically promote the expression of osteoprotegerin and receptor activator of nuclear factor kappaB ligand, but restrained the expression of receptor activator of nuclear factor kappaB (P < 0.05). These findings indicate that Kidney Chinese Herbs can dynamically regulate the osteoprotegerin-receptor activator of nuclear factor kappaB ligand-receptor activator signaling pathway, and has a positive effect to promote bone reconstruction and rehabilitation.

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: Tissue Engineering, Drugs, Chinese Herbal, Osteoclasts, Osteoblasts

CLC Number:

R318

Zeng Zhan-peng, Zhou Chi, Li Kang-huo, Wang Hai-bin, Tang Hong-yu . Osteogenesis effects and mechanisms of Kidney Chinese Herbs after fractures[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(15): 2442-2448.

Figures/Tables 4

References

[1] Lewczuk E, Biatoszewski D. The level of physical activity in patients with osteoporosis in relation to the risk and prevention of falls. Ortop Traumatol Rehabil. 2006;8(4): 412-421.
[2] Ikeda K, Takeshita S. Factors and mechanisms involved in the coupling from bone resorption to formation: how osteoclasts talk to osteoblasts. J Bone Metab. 2014;21(3): 163-167.
[3] 詹红生,赵咏芳等.用含药血清方法观察补肾接骨中药对成骨细胞功能的影响[J]中国骨伤,2001,3:54-56.
[4] Jiang SD, Jiang LS, Dai LY. Effects of spinal cord injury on osteoblastogenesis,osteoclastogenesis and gene expression profiling in osteoblasts in young rats. Osteoporos Int. 2007; 18(3): 339-349.
[5] Li CJ, Chang JK, Chou CH, et al. The PI3K/Akt/FOXO3a/ p27Kip1 signaling contributes to anti-inflammatory drug-suppressed proliferation of human osteoblasts. Biochem Pharmacol. 2010;79(6):926-937.
[6] Itoh S, Udagawa N, Takahashi N, et al. A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation. Bone. 2006;39(3): 505-512.
[7] Wu PH, Lin SK, Lee BS, et al. Epigallocatechin-3-gallate diminishes cytokine-stimulated Cyr61 expression in human osteoblastic cells: a therapeutic potential for arthritis. Rheumatology (Oxford). 2012;51(11):1953-1965.
[8] Taketa T, Sakai A, Tanaka S, et al. Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells.. J Bone Miner Metab. 2008;26(2):143-151.
[9] Hu JP, Nishishita K, Sakai E, et al. Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways . Eur J Pharmacol. 2008;580(1-2):70-79.
[10] Von Knoch F, Heckelei A, Wedemeyer C, et al. Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin. J Biomed Mater Res. 2005;75(2):288-294.
[11] Vandooren B, Cantaert T, Noordenbos T, et al. The abundant synovial expression of the RANK /RANKL/ Osteoprotegerin system in peripheral spondylarthritis is partially disconnected from inflammation. Arthritis Rheum. 2008;58(3):718-729.
[12] 欧阳露,汪选斌.中药骨碎补调节骨代谢作用及机制研究进展[J].湖北医药学院学报,2013,32(2):187-190.
[13] 赵亮,张晨.续断骨伤合剂在促进骨折愈合中对血生化指标的影响[J].湖北中医药大学学报,2011,13(1):11-13.
[14] Kreja L, Liedert A, Hasni S, et al. Mechanical regulation of osteoclastic genes in human osteoblasts. Biochem Biophys Res Commun. 2008;368(3):582-587.
[15] Taketa T, Sakai A, Tanaka S, et al. Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells. J Bone Miner Metab. 2008;26(2):143-151.
[16] Suzuki N, Yoshimura Y, Deyama Y, et al. Mechanical stress directly suppresses osteoclast differentiation in RAW264.7 cells. Int J Mol Med. 2008;21(3):291-296.
[17] Irie A, Takami M, Kubo H, et al. Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity. Bone. 2007;41(2):165-174.
[18] von Knoch F, Heckelei A, Wedemeyer C, et al. Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin. J Biomed Mater Res A. 2005;75(2):288-294.
[19] Vandooren B, Cantaert T, Noordenbos T, et al. The abundant synovial expression of the RANK/ RANKL/ Osteoprotegerin system in peripheralspondylarthritis is partially disconnected from inflammation.Arthritis Rheum. 2008;58(3):718-729.
[20] Hu JP, Nishishita K, Sakai E, et al. Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. Eur J Pharmacol. 2008;580(1-2):70-79.
[21] Makihira S, Mine Y, Kosaka E, et al. Titanium surface roughness accelerates RANKL-dependent differentiation in the osteoclast precursor cell line, RAW264.7.Dent Mater J. 2007;26(5):739-745.
[22] Poblenz AT, Jacoby JJ, Singh S, et al. Inhibition of RANKL-mediated osteoclast differentiation by selective TRAF6 decoy peptides. Biochem Biophys Res Commun. 2007;359(3):510-515.
[23] Funakoshi-Tago M, Tago K, Sonoda Y, et al. TRAF6 and C-SRC induce synergistic AP-1 activation via PI3-kinase- AKT-JNK pathway. Eur J Biochem. 2003; 270(6):1257-1268.
[24] Chandrasekar B, Mummidi S, Valente AJ, et al. The pro-atherogenic cytokine interleukin-18 induces CXCL16 expression in rat aortic smooth muscle cells via MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, c-Src, phosphatidylinositol 3-kinase, Akt, c-Jun N-terminal kinase, andactivator protein-1 signaling. J Biol Chem. 2005;280(28):26263-26277.
[25] Tsubaki M, Kato C, Manno M, et al. Macrophage inflammatory protein-1alpha (MIP-1alpha) enhances a receptor activator of nuclear factor kappaB ligand (RANKL) expression in mouse bone marrow stromal cells 22/36 and osteoblasts through MAPK and PI3K/Akt pathways. Mol Cell Biochem. 2007;304 (1-2):53-60.
[26] Pang M, Martinez AF, Fernandez I, et al. AP-1 stimulates the cathepsin K promoter in RAW 264.7 cells. Gene. 2007;403 (1-2): 151-158.
[27] Mohamed SG, Sugiyama E, Shinoda K, et al. Interleukin-10 inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos and c-Jun in RAW264.7 cells and mouse bone marrow cells. Bone. 2007;41(4):592-602.
[28] Sandur SK, Ahn KS, Ichikawa H, et al. Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products. Nutr Cancer. 2007;57(1):78-87.
[29] Hirai F, Nakayamada S, Okada Y, et al. Small GTPase Rho signaling is involved in beta1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappaB ligand on osteoblasts and osteoclast maturation. Biochem Biophys Res Commun. 2007;356(1): 279-285.
[30] Fujita K, Janz S. Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF. Mol Cancer. 2007; 6:71.
[31] Li W, Zhu S, Hu J. Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model. Clin Orthop Relat Res. 2015.
[32] Wang Z, Ding L, Zhang S, et al. Effects of icariin on the regulation of the OPG-RANKL-RANK system are mediated through the MAPK pathways in IL-1β-stimulated human SW1353 chondrosarcoma cells. Int J Mol Med. 2014;34(6): 1720-1726.
[33] Ju D, Liu M, Zhao H, et al. Mechanisms of "kidney governing bones" theory in traditional Chinese medicine. Front Med. 2014; 8(3):389-393.
[34] Irtiuga OB, Zhiduleva EV, Dubrovskaia OB, et al. Concentration of osteoprotegerin and RANKL in blood serum of patients with aortic stenosis. Kardiologiia. 2014;54(6): 44-48.
[35] Shimamura M, Nakagami H, Osako MK, et al. OPG/RANKL/RANK axis is a critical inflammatory signaling system in ischemic brain in mice. Proc Natl Acad Sci U S A. 2014;111(22):8191-8196.
[36] Liu CG, Luo QX, Ling TY, et al. Effect of Erigeron Breviscapus on the expression of OPG/RANKL/RANK in osteoblasts and pre-osteoclasts in vitro. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013;33(12):1658-1664.
[37] Zheng J, Liu JL, Lin MF, et al. Effect of modified sijunzi decoction on the bone metabolism of adriamycin induced nephropathy rats. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013; 33(10):1376-1381.
[38] Yasuda H. RANKL, a necessary chance for clinical application to osteoporosis and cancer-related bone diseases. World J Orthop. 2013;4(4):207-217.
[39] Wang J, Chen TY, Qin S, et al. Inhibitory effect of metformin on bone metastasis of cancer via OPG/RANKL/RANK system. Med Hypotheses. 2013;81(5):805-806.
[40] Szymczak J, Bohdanowicz-Pawlak A. Osteoprotegerin, RANKL, and bone turnover in primary hyperparathyroidism: the effect of parathyroidectomy and treatment with alendronate. Horm Metab Res. 2013;45(10):759-764.