Effects of JSOG-6 on protection against bone loss in ovariectomized mice through regulation of osteoblast differentiation and osteoclast formation

BMC Complementary and Alternative Medicine

Sang Kook Lee²  Hyen Joo Park²  In-Hyuk Ha¹  Jinho Lee¹  Joon-Shik Shin¹  Lan Cho²  Hwa-Jin Chung² 

[1]Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Jaseng Hospital of Korean Medicine, Seoul 135-896, Korea

[2]College of Pharmacy, Natural Products Research Institute, Seoul National University, San 56-1 Sillim-dong, Gwanak-gu, Seoul 151-742, Korea

关键词: Osteoblast;    Osteoclast;    Bone loss;    Ovariectomized mice;    JSOG-6;   

Others  :  1220109
DOI  :  10.1186/1472-6882-14-184

 received in 2013-12-13, accepted in 2014-05-29,  发布年份 2014

【 摘 要 】

Background

JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action.

Methods

Protection against bone loss was assessed in an ovariectomized (OVX) mouse model. Bone microarchitecture was measured using a micro-computed tomography to detect the parameters of three-dimensional structure of a trabecular bone. Serum biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed to investigate the mechanism of action.

Results

Oral administration of JSOG-6 significantly increased the bone mineral density (BMD) of the femur in OVX mice in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group was significantly recovered by JSOG-6 treatment. The serum levels of alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase, biomarkers of bone resorption, were significantly elevated in OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was also found to enhance the osteoblastic differentiation and maturation with the increase of the density and ALP activity, a marker of osteoblastic differentiation, as well as calcium deposition, a marker of osteoblastic maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic differentiation were also associated in part with the increase of ALP and OPN mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells.

Conclusions

The findings demonstrate that JSOG-6 induced protection against bone loss in OVX mice, and its anti-osteoporotic property might be, in part, a function of the stimulation of osteoblast differentiation and the inhibition of osteoclast formation. These findings suggest that JSOG-6 might be an applicable therapeutic traditional medicine for the regulation of the osteoporotic response.

【 授权许可】

   
2014 Chung et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Alexander JM, Bab I, Fish S, Müller R, Uchiyama T, Gronowicz G, Nahounou M, Zhao Q, White DW, Chorev M, Gazit D, Rosenblatt M: Human parathyroid hormone 1–34 reverses bone loss in ovariectomized mice. J Bone Miner Res 2001, 161:665-673.
• [2]Raisz LG: Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005, 115:3318-3325.
• [3]Takayanagi H: Inflammatory bone destruction and osteoimmunology. J Periodontal Res 2005, 40:287-293.
• [4]Papachroni KK, Karatzas DN, Papavassiliou KA, Basdra EK, Papavassiliou AG: Mechanotransduction in osteoblast regulation and bone disease. Trends Mol Med 2009, 15:208-216.
• [5]Harada S, Rodan GA: Control of osteoblast function and regulation of bone mass. Nature 2003, 15:349-355.
• [6]Rahman MM, Bhattacharya A, Fernandes G: Conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling. J Lipid Res 2006, 47:1739-1748.
• [7]Rodan GA, Martin TJ: Therapeutic approaches to bone diseases. Science 2000, 289:1508-1514.
• [8]Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999, 20:345-357.
• [9]Teitelbaum SL: Bone resorption by osteoclasts. Science 2000, 289:1504-1508.
• [10]Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003, 423:337-342.
• [11]Martin TJ: Historically significant events in the discovery of RANK/RANKL/OPG. World J Orthop 2013, 4:186-197.
• [12]Hadjidakis DJ, Androulakis II: Bone remodeling. Ann N Y Acad Sci 2006, 1092:385-396.
• [13]Inaba K, Murata K, Naruto S, Matsuda H: Inhibitory effects of devil’s claw (secondary root of Harpagophytum procumbens) extract and harpagoside on cytokine production in mouse macrophages. J Nat Med 2012, 64:219-222.
• [14]Sanders M, Grundmann O: The use of glucosamine, devil’s claw (Harpagophytum procumbens), and acupuncture as complementary and alternative treatments for osteoarthritis. Altern Med Rev 2011, 16:228-238.
• [15]Fiebich BL, Muñoz E, Rose T, Weiss G, McGregor GP: Molecular targets of the antiinflammatory Harpagophytum procumbens (devil’s claw): inhibition of TNFα and COX-2 gene expression by preventing activation of AP-1. Phytother Res 2012, 26:806-811.
• [16]Chen LL, Lei LH, Ding PH, Tang Q, Wu YM: Osteogenic effect of Drynariae rhizoma extracts and Naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Arch Oral Biol 2011, 56:1655-1662.
• [17]Anuja GI, Latha PG, Suja SR, Shyamal S, Shine VJ, Sini S, Pradeep S, Shikha P: Rajasekharan S. Anti-inflammatory and analgesic properties of Drynaria quercifolia (L.) J. Smith. J Ethnopharmacol 2010, 11:456-460.
• [18]Nukaya H, Yamashiro H, Fukazawa H, Ishida H, Tsuji K: Isolation of inhibitors of TPA-induced mouse ear edema from Hoelen, Poria cocos. Chem Pharm Bull 1996, 44:847-849.
• [19]Han Y, Jung HW, Lee JY, Kim JS, Kang SS, Kim YS, Park YK: 2,5-dihydroxyacetophenone isolated from Rehmanniae Radix Preparata inhibits inflammatory responses in lipopolysaccharide-stimulated RAW264.7 macrophages. J Med Food 2012, 15:505-510.
• [20]Kim HR, Cui Y, Hong SJ, Shin SJ, Kim DS, Kim NM, So SH, Lee SK, Kim EC, Chae SW, Chae HJ: Effect of ginseng mixture on osteoporosis in ovariectomized rats. Immunopharmacol Immunotoxicol 2008, 30:333-345.
• [21]Zhang Y, Lai WP, Leung PC, Wu CF, Wong MS: Short- to mid-term effects of ovariectomy on bone turnover, bone mass and bone strength in rats. Biol Pharm Bull 2007, 30:898-903.
• [22]Chen WF, Wong MS: Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells. Br J Nutr 2006, 95:1039-1047.
• [23]Bhargavan B, Gautam AK, Singh D, Kumar A, Chaurasia S, Tyagi AM, Yadav DK, Mishra JS, Singh AB, Sanyal S, Goel A, Maurya R, Chattopadhyay N: Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. J Cell Biochem 2009, 1:388-399.
• [24]Takahashi N, Yamada H, Yosiki S, Roodman GD, Mundy GR, Jones SJ, Boyde A, Suda T: Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 1998, 122:1373-1382.
• [25]Katagiri T, Yamaguchi A, Ikeda T, Yoshiki S, Wozney JM, Rosen V, Wang EA, Tanaka H, Omura S, Suda T: The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun 1990, 172:295-299.
• [26]Yamaguchi A, Katagiri T, Ikeda T, Wozney JM, Rosen V, Wang EA, Kahn AJ, Suda T, Yoshiki S: Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 1991, 113:681-687.
• [27]Hohenhaus MH, McGarry KA, Col NF: Hormone therapy for the prevention of bone loss in menopausal women with osteopenia: is it a viable option? Drugs 2007, 67:2311-2321.
• [28]Levine JP: Effective strategies to identify postmenopausal women at risk for osteoporosis. Geriatrics 2007, 62:22-30.
• [29]Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S: Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate. Bone 1996, 18:621-627.
• [30]Sato M, Bryant HU, Iversen P, Helterbrand J, Smietana F, Bemis K, Higgs R, Turner CH, Owan I, Takano Y, Burr DB: Advantages of raloxifene over alendronate or estrogen on nonreproductive and reproductive tissues in the long-term dosing of ovariectomized rats. J Pharmacol Exp Ther 1996, 279:298-305.
• [31]Cano A, Dapía S, Noguera I, Pineda B, Hermenegildo C, del Val R, Caeiro JR, García-Pérez MA: Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice. Osteoporos Int 2008, 19:793-800.
• [32]Bahlous A, Kalai E, Hadj Salah M, Bouzid K, Zerelli L: Biochemical markers of bone remodeling: recent data of their applications in managing postmenopausal osteoporosis. Tunis Med 2006, 84:751-757.
• [33]Owen TA, Aronow MS, Barone LM, Bettencourt B, Stein GS, Lian JB: Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology 1991, 128:1496-1504.
• [34]Stein GS, Lian JB: Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 1993, 14:424-442.
• [35]Suda K, Woo J-T, Takami M, Sexton PM, Nagai K: Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-α, IL-1, and RANKL. J Cell Physiol 2002, 190:101-108.
• [36]Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K: Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): amechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998, 139:1329-1337.
• [37]Teitelbaum SL: Osteoclasts, integrins, and osteoporosis. J Bone Miner Metab 2000, 18:344-349.
• [38]Bord S, Ireland DC, Beavan SR, Compston JE: The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 2003, 32:136-141.
• [39]Hu Y, Chan E, Wang SX, Li B: Activation of p38 mitogen-activated protein kinase is equired for osteoblast differentiation. Endocrinology 2003, 144:2068-2074.
• [40]Jadlowiec J, Koch H, Zhang X, Campbell PG, Seyedain M, Sfeir C: Phosphophoryn regulates the gene expression and differentiation of NIH3T3, MC3T3-E1, and human mesenchymal stem cells via the integrin/MAPK signaling pathway. J Biol Chem 2004, 17:53323-53330.
• [41]Ross FP, Teitelbaum SL: Alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev 2005, 208:88-105.
• [42]Takayanagi H, Sato K, Takaoka A, Taniguchi T: Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 2005, 208:181-193.
• [43]Khosla S: Minireview: the OPG/RANKL/RANK system. Endocrinology 2001, 142:5050-5055.