Tougu Xiaotong capsule exerts a therapeutic effect by improving knee meniscus in the early osteoarthritis rat model

Wu,Guangwen; Huang,Yunmei; Chen,Wenlie; Chen,Junfang; Lu,Xiaodong; Liu,Xiangxiang; Feng,Fangfang; Huang,Meiya; Lin,Ruhui; Li,Zuanfang; Tan,Chunjiang

doi:10.3892/etm.2020.8624

Tougu Xiaotong capsule exerts a therapeutic effect by improving knee meniscus in the early osteoarthritis rat model

Authors:
- Guangwen Wu
- Yunmei Huang
- Wenlie Chen
- Junfang Chen
- Xiaodong Lu
- Xiangxiang Liu
- Fangfang Feng
- Meiya Huang
- Ruhui Lin
- Zuanfang Li
- Chunjiang Tan
View Affiliations

Affiliations: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China, National Laboratory of Traditional Chinese Medicine Pharmacology (Cell Structure and Function), Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
Published online on: March 24, 2020 https://doi.org/10.3892/etm.2020.8624
Pages: 3641-3649
Copyright: © Wu 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

The aim of the study was to observe the effects of Tougu Xiaotong capsule (TGXTC) on the microstructure and ultrastructure of meniscus in rats with early knee osteoarthritis (KOA). A total of 27 Sprague Dawley rats were randomly divided into three groups: The normal group (non-papain-induced KOA; received saline only), the model group (papain-induced KOA; received saline only) and the TGXTC group [papain-induced KOA; received TGXTC (0.31g·kg-1·d-1)]. After 4 weeks treatment, the animals were anesthetized and the sagittal plane of the intact knees (n=6 per group) was obtained and prepared in paraffin section. Following hematoxylin and eosin staining, the degeneration of cartilage structure was evaluated via Mankin score, the microstructure of meniscus was observed and the area of calcification in meniscus was analyzed. Following toluidine blue staining, the content of proteoglycan in meniscus was analyzed. Three samples in each group were obtained and the ultrathin sections of meniscus were observed through a transmission electron microscope. The results showed that compared with the normal group, in the model group the joint space became narrow and the cartilage layer was slightly damaged and the Mankin score was 4.17±0.76, suggesting that the early KOA model was successfully established. After TGXTC treatment, the joint space stenosis and cartilage damage were improved as the Mankin score significantly decreased. Compared with the normal group, in the model group the surface of meniscal cartilage was much more uneven, the area of calcification was significantly increased and the content of proteoglycan of cartilage matrix was significantly decreased. However, following TGXTC treatment, the surface of the meniscal cartilage was much more smooth and flat, and the damage of tissue structure and the calcified area were significantly reduced, and the proteoglycan of cartilage matrix content was significantly increased. Compared with the normal group, the number of cellular processes and organelles, including the rough endoplasmic reticulum, mitochondria and Golgi apparatus of meniscal cartilage were reduced and swollen in the model group. In addition, the nuclei were deformed and heterochromatin agglutinated. The extracellular collagen fibrils became slender, disordered and sparse. Compared with the model group, the TGXTC group had more cell processes and organelles, alleviated swelling and heterochromatin agglutinating. Additionally, the collagen fibrils around the cells were thicker, larger and arranged in an orderly manner. In conclusion, TGXTC exerted its therapeutic effects on the development of KOA via reducing the destruction of the cartilage structure of the meniscus and improving the composition and function of the meniscus cartilage matrix.

View Figures

View References

1	Kettelkamp DB and Jacobs AW: Tibiofemoral contact area - determination and implications. J Bone Joint Surg Am. 54:349–356. 1972.PubMed/NCBI
2	Seedhom BB: Loadbearing function of the menisci. Physiotherapy. 62(223)1976.PubMed/NCBI
3	Seedhom BB and Hargreaves DJ: Transmission of the load in the knee joint with special reference to the role in the menisci: Part II. Experimental results, discussion and conclusion. Eng Med. 8:220–228. 1979.
4	Ahmed AM and Burke DL: In-vitro measurement of static pressure distribution in synovial joints - Part I: Tibial surface of the knee. J Biomech Eng. 105:216–225. 1983.PubMed/NCBI View Article : Google Scholar
5	Mow VC, Gu WY and Chen HC: Structure and function of articular cartilage and meniscus. In: Basic Orthopaedic Biomechanics and Mechano-Biology. 3rd edition. Mow VC and Huiskes R (eds). Lippincott Williams & Wilkins, Philadelphia, 2005.
6	McDermott ID, Masouros SD and Amis AA: Biomechanics of the menisci of the knee. Curr Orthop. 22:193–201. 2008.PubMed/NCBI View Article : Google Scholar
7	Chevrier A, Nelea M, Hurtig MB, Hoemann CD and Buschmann MD: Meniscus structure in human, sheep, and rabbit for animal models of meniscus repair. J Orthop Res. 27:1197–1203. 2009.PubMed/NCBI View Article : Google Scholar
8	Englund M, Guermazi A and Lohmander LS: The meniscus in knee osteoarthritis. Rheum Dis Clin North Am. 35:579–590. 2009.PubMed/NCBI View Article : Google Scholar
9	Fox AJ, Wanivenhaus F, Burge AJ, Warren RF and Rodeo SA: The human meniscus: A review of anatomy, function, injury, and advances in treatment. Clin Anat. 28:269–287. 2015.PubMed/NCBI View Article : Google Scholar
10	Fox AJ, Bedi A and Rodeo SA: The basic science of human knee menisci: Structure, composition, and function. Sports Health. 4:340–351. 2012.PubMed/NCBI View Article : Google Scholar
11	Rath E and Richmond JC: The menisci: Basic science and advances in treatment. Br J Sports Med. 34:252–257. 2000.PubMed/NCBI View Article : Google Scholar
12	Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J and Jordan KP: Current evidence on risk factors for knee osteoarthritis in older adults: A systematic review and meta-analysis. Osteoarthritis Cartilage. 23:507–515. 2015.PubMed/NCBI View Article : Google Scholar
13	Muthuri SG, McWilliams DF, Doherty M and Zhang W: History of knee injuries and knee osteoarthritis: A meta-analysis of observational studies. Osteoarthritis Cartilage. 19:1286–1293. 2011.PubMed/NCBI View Article : Google Scholar
14	Liao N, Huang Y, Ye J, Chen W, Li ZF, Lin R, Li X, Zheng L and Liu X: Protective effects of Tougu Xiaotong capsule on tumor necrosis factor-α-injured UMR-106 cells. Exp Ther Med. 10:1908–1914. 2015.PubMed/NCBI View Article : Google Scholar
15	Chen S, Huang Y, Chen W, Wu G, Liao N, Li X, Huang M, Lin R, Yu C, Li X, et al: Protective effects of the Tougu Xiaotong capsule on morphology and osteoprotegerin/nuclear factor-κB ligand expression in rabbits with knee osteoarthritis. Mol Med Rep. 13:419–425. 2016.PubMed/NCBI View Article : Google Scholar
16	Zheng CS, Ye HZ, Xu XJ and Liu XX: Computational pharmacology study of tougu xiaotong granule in preventing and treating knee osteoarthritis. Chin J Integr Med. 15:371–376. 2009.PubMed/NCBI View Article : Google Scholar
17	Lin MN and Liu XX: Observation of Tougu Xiaotong Recipe for the treatment of 30 patients with knee osteoarthritis. Fujian J Tradit Chin Med Chin. 36:15–16, 20 (In Chinese).
18	Li XH, Wu MX, Ye HZ, Chen WL, Lin JM, Zheng LP and Liu XX: Experimental study on the suppression of sodium nitroprussiate-induced chondrocyte apoptosis by Tougu Xiaotong Capsule-containing serum. Chin J Integr Med. 17:436–443. 2011.PubMed/NCBI View Article : Google Scholar
19	Li X, Lang W, Ye H, Yu F, Li H, Chen J, Cai L, Chen W, Lin R, Huang Y, et al: Tougu Xiaotong capsule inhibits the tidemark replication and cartilage degradation of papain-induced osteoarthritis by the regulation of chondrocyte autophagy. Int J Mol Med. 31:1349–1356. 2013.PubMed/NCBI View Article : Google Scholar
20	Wu G, Zhang J, Chen W, Chen S, Huang Y, Lin R, Huang M, Li Z, Zheng L and Li X: Tougu Xiaotong capsule exerts a therapeutic effect on knee osteoarthritis by regulating subchondral bone remodeling. Mol Med Rep. 19:1858–1866. 2019.PubMed/NCBI View Article : Google Scholar
21	Mankin HJ, Dorfman H, Lippiello L and Zarins A: Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 53:523–537. 1971.PubMed/NCBI
22	Tan C, Zhang J, Chen W, Feng F, Yu C, Lu X, Lin R, Li Z, Huang Y, Zheng L, et al: Inflammatory cytokines via upregulation of aquaporins deteriorated the pathogenesis of early osteoarthritis. PLoS ONE. 14(e0220846): https://doi.org/10.1371/journal.pone.0220846. 2019.PubMed/NCBI View Article : Google Scholar
23	Aaron RK, Racine J and Dyke JP: Contribution of circulatory disturbances in subchondral bone to the pathophysiology of osteoarthritis. Curr Rheumatol Rep. 19(49)2017.PubMed/NCBI View Article : Google Scholar
24	Hügle T and Geurts J: What drives osteoarthritis?-synovial versus subchondral bone pathology. Rheumatology (Oxford). 56:1461–1471. 2017.PubMed/NCBI View Article : Google Scholar
25	Griffin TM and Guilak F: The role of mechanical loading in the onset and progression of osteoarthritis. Exerc Sport Sci Rev. 33:195–200. 2005.PubMed/NCBI View Article : Google Scholar
26	Guilak F, Fermor B, Keefe FJ, Kraus VB, Olson SA, Pisetsky DS, Setton LA and Weinberg JB: The role of biomechanics and inflammation in cartilage injury and repair. Clin Orthop Relat Res. 423:17–26. 2004.PubMed/NCBI View Article : Google Scholar
27	Beaufils P and Pujol N: Management of traumatic meniscal tear and degenerative meniscal lesions. Save the meniscus. Orthop Traumatol Surg Res. 103 (8S):S237–S244. 2017.PubMed/NCBI View Article : Google Scholar
28	Vaquero J and Forriol F: Meniscus tear surgery and meniscus replacement. Muscles Ligaments Tendons J. 6:71–89. 2016.PubMed/NCBI View Article : Google Scholar
29	Makris EA, Hadidi P and Athanasiou KA: The knee meniscus: Structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials. 32:7411–7431. 2011.PubMed/NCBI View Article : Google Scholar
30	Ghazi ZL, Chevrier A, Farr J, Rodeo SA and Buschmann MD: Augmentation techniques for meniscus repair. J Knee Surg. 31:99–116. 2018.PubMed/NCBI View Article : Google Scholar
31	Guo W, Xu W, Wang Z, Chen M, Hao C, Zheng X, Huang J, Sui X, Yuan Z, Zhang Y, et al: Cell-free strategies for repair and regeneration of meniscus injuries through the recruitment of endogenous stem/progenitor cells. Stem Cells Int. 2018(5310471)2018.PubMed/NCBI View Article : Google Scholar
32	Pillai MM, Gopinathan J, Selvakumar R and Bhattacharyya A: human knee meniscus regeneration strategies: A review on recent advances. Curr Osteoporos Rep. 16:224–235. 2018.PubMed/NCBI View Article : Google Scholar
33	Cheng T, Wang Q, Zhou J and Wen J: Clinical study of internal traditional chinese medicine on functional recovery after sugery under arthroscope for meniscus injury treatment. Chin J Trad Med Traum Orthop. 23:27–30. 2015.(In Chinese).
34	Tang HY: Effect of compound longxuejie powder in the acute phase of meniscus injury. China Health Stand Manage. 7:150–151. 2016.(In Chinese).
35	Song SF and Li BH: Effects of Jiawei Huoxue Xiaozhong Decoction on VAS Score and Knee Joint Function in Meniscus Injury after Arthroscopic Meniscus suture. Med J Liaoning. 31:52–54. 2017.(In Chinese).
36	Gallo MC, Wyatt C, Pedoia V, Kumar D, Lee S, Nardo L, Link TM, Souza RB and Majumdar S: T1ρ and T2 relaxation times are associated with progression of hip osteoarthritis. Osteoarthritis Cartilage. 24:1399–1407. 2016.PubMed/NCBI View Article : Google Scholar
37	Englund M, Guermazi A, Roemer F W, Aliabadi P, Yang M, Lewis CE, Torner J, Nevitt MC, Sack B and Felson DT: Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle-aged and elderly persons: The Multicenter Osteoarthritis Study. Arthritis Rheum. 60:831–839. 2014.