Ajuga decumbens stimulates mesenchymal stem cell differentiation and regenerates cartilage in a rabbit osteoarthritis model

Sawada,Yoko; Sugimoto,Atsushi; Osaki,Tomohiro; Okamoto,Yoshiharu

doi:10.3892/etm.2018.5981

Ajuga decumbens stimulates mesenchymal stem cell differentiation and regenerates cartilage in a rabbit osteoarthritis model

Authors:
- Yoko Sawada
- Atsushi Sugimoto
- Tomohiro Osaki
- Yoshiharu Okamoto
View Affiliations

Affiliations: Technology Research and Development Laboratory, Research and Development Headquarters, Asahi Group Foods, Ltd., Moriya‑shi, Ibaraki 302‑0106, Japan, Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680‑8553, Japan
Published online on: March 21, 2018 https://doi.org/10.3892/etm.2018.5981
Pages: 4080-4088
Copyright: © Sawada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In a previous study by our group, Ajuga decumbens extract (ADE) was demonstrated to decrease the number of osteoclasts in subchondral bone and to have a synergistic effect with glucosamine in improving cartilaginous injuries in a rabbit model of osteoarthritis. In the present study, a concentrate of the useful fraction of ADE, termed extra ADE (EADE), which includes higher concentrations of the active component 20‑hydroxyecdysone, was evaluated for its efficacy to accelerate the healing of experimental cartilage injury. Cartilage injuries were surgically induced in rabbits by creating three holes; one in the articular cartilage of the medial trochlea and two in the trochlear sulcus of the distal femur. The rabbits were divided into the following four groups (n=3 in each): Control, ADE (0.5 g/kg), low dosage EADE (0.05 g/kg; low EADE) and high dosage EADE (0.5 g/kg; high EADE). ADE and EADE were dissolved in tap water and each dosage was orally administered every day for 3 weeks. At the end of the experimental period, histological analysis indicated that the cartilage matrix was regenerated in the low and high EADE groups. On counting of cells in the histological specimens, it was determined that the mean number of osteoclasts per 100 osteoblasts in subchondral bone was lower in the high EADE group compared with the control group. Furthermore, the results indicated that treatment with EADE (1‑100 µg/ml) stimulated chondrogenic differentiation of mesenchymal stem cells and induced proteoglycan production to a greater extent than the control in vitro. EADE treatment (10 and 100 µg/ml) was also observed to significantly attenuate interleukin‑1β‑induced prostaglandin E2 production in chondrocytes (P<0.05). In summary, the results of the present study suggest that EADE may have greater curative effects on bone injury compared with the currently used therapeutic ADE.

View Figures

View References

1	Yoshimura N, Muraki S, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Yoshida H, Suzuki T, Yamamoto S, et al: Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: The research on osteoarthritis/osteoporosis against disability study. J Bone Miner Metab. 27:620–628. 2009. View Article : Google Scholar : PubMed/NCBI
2	Buckwalter JA, Martin J and Mankin HJ: Synovial joint degeneration and the syndrome of osteoarthritis. Instr Course Lect. 49:481–489. 2000.PubMed/NCBI
3	Buckwalter JA, Roughley PJ and Rosenberg LC: Age-related changes in cartilage proteoglycans: Quantitative electron microscopic studies. Microsc Res Tech. 28:398–408. 1994. View Article : Google Scholar : PubMed/NCBI
4	Martin JA and Buckwalter JA: Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthop J. 21:1–7. 2001.PubMed/NCBI
5	Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE and Gossett C: Long-term effects of glucosamine sulphate on osteoarthritis progression: A randomised, placebo-controlled clinical trial. Lancet. 357:251–256. 2001. View Article : Google Scholar : PubMed/NCBI
6	Nakamura H, Shibakawa A, Tanaka M, Kato T and Nishioka K: Effects of glucosamine hydrochloride on the production of prostaglandin E2, nitric oxide and metalloproteases by chondrocytes and synoviocytes in osteoarthritis. Clin Exp Rheumatol. 22:293–299. 2004.PubMed/NCBI
7	Tamai Y, Miyatake K, Okamoto Y, Takamori Y, Sakamoto H and Minami S: Enhanced healing of cartilaginous injuries by glucosamine hydrochloride. Carbohydr Polym. 48:369–378. 2002. View Article : Google Scholar
8	Naito K, Watari T, Furuhata A, Yomogida S, Sakamoto K, Kurosawa H, Kaneko K and Nagaoka I: Evaluation of the effect of glucosamine on an experimental rat osteoarthritis model. Life Sci. 86:538–543. 2010. View Article : Google Scholar : PubMed/NCBI
9	Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO III, Weisman MH, Jackson CG, et al: Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 354:795–808. 2006. View Article : Google Scholar : PubMed/NCBI
10	Ono Y, Fukaya Y, Imai S and Yamakuni T: Beneficial effects of Ajuga decumbens on osteoporosis and arthritis. Biol Pharm Bull. 31:1199–1204. 2008. View Article : Google Scholar : PubMed/NCBI
11	Sawada Y, Sugimoto A, Fukuda K, Kurosawa T, Ogawa M, Osaki T and Minami S: Oral administration of Ajuga decumbens extract has a synergetic effect with glucomsaine on cartilaginous injury in a rabbit osteoaruthritis model. J Chitin Chitosan Sci. 2:191–196. 2014. View Article : Google Scholar
12	Kapur P, Wuttke W, Jarry H and Seidlova-Wuttke D: Beneficial effects of beta-Ecdysone on the joint, epiphyseal cartilage tissue and trabecular bone in ovariectomized rats. Phytomedicine. 17:350–355. 2010. View Article : Google Scholar : PubMed/NCBI
13	Mardones R, Jofré CM and Minguell JJ: Cell therapy and tissue engineering approaches for cartilage repair and/or regeneration. Int J Stem Cells. 8:48–53. 2015. View Article : Google Scholar : PubMed/NCBI
14	Ham O, Lee CY, Kim R, Lee J, Oh S, Lee MY, Kim J, Hwang KC, Maeng LS and Chang W: Therapeutic potential of differentiated mesenchymal stem cells for treatment of osteoarthritis. Int J Mol Sci. 16:14961–14978. 2015. View Article : Google Scholar : PubMed/NCBI
15	Johnson K, Zhu S, Tremblay MS, Payette JN, Wang J, Bouchez LC, Meeusen S, Althage A, Cho CY, Wu X and Schultz PG: A stem cell-based approach to cartilage repair. Science. 336:717–721. 2012. View Article : Google Scholar : PubMed/NCBI
16	Osaki T, Kitahara K, Okamoto Y, Imagawa T, Tsuka T, Miki Y, Kawamoto H, Saimoto H and Minami S: Effect of fucoidan extracted from mozuku on experimental cartilaginous tissue injury. Mar Drugs. 10:2560–2570. 2012. View Article : Google Scholar : PubMed/NCBI
17	Rodan G: Introduction to bone biology. Bone. 13 Suppl 1:S3–S6. 1992. View Article : Google Scholar : PubMed/NCBI
18	Gao L, Cai G and Shi X: Beta-ecdysterone induces osteogenic differentiation in mouse mesenchymal stem cells and relieves osteoporosis. Biol Pharm Bull. 31:2245–2249. 2008. View Article : Google Scholar : PubMed/NCBI
19	Hashida M, Miyatake K, Okamoto Y, Fujita K, Matsumoto T, Morimatsu F, Sakamoto K and Minami S: Synergistic effects of D-glucosamine and collagen peptides on healing experimental cartilage injury. Macromol Biosci. 3:596–603. 2003. View Article : Google Scholar
20	Derfoul A, Miyoshi AD, Freeman DE and Tuan RS: Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation. Osteoarthritis Cartilage. 15:646–655. 2007. View Article : Google Scholar : PubMed/NCBI
21	Farahat MN, Yanni G, Poston R and Panayi GS: Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 52:870–875. 1993. View Article : Google Scholar : PubMed/NCBI
22	Campbell IK, Piccoli DS and Hamilton JA: Stimulation of human chondrocyte prostaglandin E2 production by recombinant human interleukin-1 and tumour necrosis factor. Biochim Biophys Acta. 1051:310–318. 1990. View Article : Google Scholar : PubMed/NCBI
23	Tetlow LC, Adlam DJ and Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: Associations with degenerative changes. Arthritis Rheum. 44:585–594. 2001. View Article : Google Scholar : PubMed/NCBI
24	Sheu SY, Ho SR, Sun JS, Chen CY and Ke CJ: Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β-induced catabolic gene expression in cartilage. BMC Complement Altern Med. 15:12015. View Article : Google Scholar : PubMed/NCBI
25	Kotake S, Yago T, Kawamoto M and Nanke Y: Effects of NSAIDs on differentiation and function of human and murine osteoclasts-crucial ‘human osteoclastology’. Pharmaceuticals (Basel). 3:1394–1410. 2010. View Article : Google Scholar : PubMed/NCBI