Research Article

Acupotomy inhibits aberrant formation of subchondral bone through regulating osteoprotegerin/receptor activator of nuclear factor-κB ligand pathway in rabbits with knee osteoarthritis induced by modified Videman method

  • Luxue QIN ,
  • Changqing GUO ,
  • Ruili ZHAO ,
  • Tong WANG ,
  • Junmei WANG ,
  • Yan GUO ,
  • Wei ZHANG ,
  • Tingyao HU ,
  • Xilin CHEN ,
  • Qian ZHANG ,
  • Dian ZHANG ,
  • Yue XU
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  • 1 School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China
    2 the First People's Hospital of Dongcheng District, Beijing 100050, China
    3 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
    4 the Third Affiliated Hospital of Beijing Universality of Chinese Medicine, Beijing 100029, China
Prof. GUO Changqing, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China. Guochangqing66@163.com,Telephone: +86-10-64286687

Received date: 2021-10-22

  Accepted date: 2022-12-01

  Online published: 2022-05-20

Supported by

Beijing Municipal Natural Science Foundation: To Explore the Effect of Acupotomy on Subchondral Bone Remodeling in Early and Middle KOA Based on OPG/RANKL/RANK pathway(7192110)

Abstract

OBJECTIVE: To investigate the effects of acupotomy on inhibiting abnormal formation of subchondral bone in rabbits with knee osteoarthritis (KOA).

METHODS: A total of 24 New Zealand rabbits were randomly divided into four groups of 6 rabbits each [control, model, electroacupuncture (EA) and acupotomy]. Eighteen KOA model rabbits were established using a modified Videman method. Rabbits in EA and acupotomy groups received the intervention for 3 weeks. Then, the cartilage and subchondral bone unit were obtained and the histomorphological changes were recorded. Osteo-protegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in subchondral bone were evaluated by Western blotting, real-time polymerase chain reaction and immunohistochemistry.

RESULTS: Compared with the model group, both the acupotomy and EA groups showed a significant decrease in the Lequesne index (both P < 0.01) and Mankin score (P < 0.01, < 0.05). In addition, both EA and acupotomy groups had a higher expression of total articular cartilage (TAC) (P < 0.05, < 0.01) and lower expression of articular calcified cartilage (ACC)/TAC (P < 0.05, < 0.05) compared with the model group. The thickness of the subchondral bone plate in EA and acupotomy groups were decreased (both P < 0.01) compared to the model group. Moreover, trabecular bone volume (BV/TV), protein and relative expression of OPG and the ratio of OPG/RANKL in the subchondral bone of acupotomy group were decreased statistically significant, while these parameters were not significantly changed in the EA group compared with the model group.

CONCLUSIONS: In the rabbit model of KOA, acupotomy inhibits aberrant formation of subchondral bone by suppressing OPG/RANKL ratio as a potential therapy for KOA.

Cite this article

Luxue QIN , Changqing GUO , Ruili ZHAO , Tong WANG , Junmei WANG , Yan GUO , Wei ZHANG , Tingyao HU , Xilin CHEN , Qian ZHANG , Dian ZHANG , Yue XU . Acupotomy inhibits aberrant formation of subchondral bone through regulating osteoprotegerin/receptor activator of nuclear factor-κB ligand pathway in rabbits with knee osteoarthritis induced by modified Videman method[J]. Journal of Traditional Chinese Medicine, 2022 , 42(3) : 389 -399 . DOI: 10.19852/j.cnki.jtcm.2022.03.006

References

1 Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380:2163-96.
2 Lane NE, Shidara K, Wise BL. Osteoarthritis year in review 2016: clinical. Osteoarthritis Cartilage 2017; 25:209-15.
3 Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: the chronic osteoarthritis management initiative of the U.S. bone and joint initiative. Semin Arthritis Rheum 2014; 43:701-12.
4 Hugle T, Geurts J. What drives osteoarthritis-synovial versus subchondral bone pathology. Rheumatology (Oxford) 2017; 56:1461-71.
5 Iijima H, Aoyama T, Ito A, et al. Immature articular cartilage and subchondral bone covered by menisci are potentially susceptive to mechanical load. BMC Musculoskelet Disord 2014; 15:101.
6 Chen X, Wang ZQ, Duan N, Zhu GY, Schwarz EM, Xie C. Osteoblast-osteoclast interactions. Connect Tissue Res 2018; 59:99-107.
7 Zhen G, Wen C, Jia XF, et al. Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 2013; 19:704-12.
8 Holzer LA, Kraiger M, Talakic E, et al. Microstructural analysis of subchondral bone in knee osteoarthritis. Osteoporos Int 2020; 31:2037-45.
9 Findlay DM, Atkins GJ. Osteoblast-chondrocyte interactions in osteoarthritis. Curr Osteoporos Rep 2014; 12:127-34.
10 Bellido M, Lugo L, Roman-Blas JA, et al. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther 2010; 12:R152.
11 Schaffler MB, Kennedy OD. Osteocyte signaling in bone. Curr Osteoporos Rep 2012; 10:118-25.
12 Zhou XC, Cao H, Yuan Y, Wu W. Biochemical Signals Mediate the Crosstalk between Cartilage and Bone in Osteoarthritis. Biomed Res Int 2020; 2020:5720360.
13 Felson DT. Osteoarthritis as a disease of mechanics. Osteoarthritis Cartilage 2013; 21:10-5.
14 Lin M, Li X, Liang WN, et al. Needle-knife therapy improves the clinical symptoms of knee osteoarthritis by inhibiting the expression of inflammatory cytokines. Exp Ther Med 2014; 7:835-42.
15 Ma SN, Xie ZG, Guo Y, et al. Effect of acupotomy on FAK-PI3K signaling pathways in KOA rabbit articular cartilages. Evid Based Complement Alternat Med 2017; 2017:4535326.
16 Liang CX, Guo Y, Tao L, et al. Effects of acupotomy intervention on regional pathological changes and expression of cartilage-mechanics related proteins in rabbits with knee osteoarthritis. Zhen Ci Yan Jiu 2015; 40:119-24, 140.
17 Langenskiold A, Michelsson JE, Videman T. Osteoarthritis of the knee in the rabbit produced by immobilization. Attempts to achieve a reproducible model for studies on pathogenesis and therapy. Acta Orthop Scand 1979; 50:1-14.
18 Nagira K, Ikuta Y, Shinohara M, et al. Histological scoring system for subchondral bone changes in murine models of joint aging and osteoarthritis. Sci Rep 2020; 10:10077.
19 Mitchell RE, Huitema LF, Skinner RE, et al. New tools for studying osteoarthritis genetics in zebrafish. Osteoarthritis Cartilage 2013; 21:269-78.
20 Samvelyan HJ, Hughes D, Stevens C, Staines KA. Models of osteoarthritis: relevance and new insights. Calcif Tissue Int 2021; 109:243-56.
21 Li W, Lin JJ, Wang ZW, et al. Bevacizumab tested for treatment of knee osteoarthritis via inhibition of synovial vascular hyperplasia in rabbits. J Orthop Translat 2019; 19:38-46.
22 Matsui H, Shimizu M, Tsuji H. Cartilage and subchondral bone interaction in osteoarthrosis of human knee joint: a histological and histomorphometric study. Microsc Res Tech 1997; 37:333-42.
23 Finnila M, Thevenot J, Aho OM, et al. Association between subchondral bone structure and osteoarthritis histopathological grade. J Orthop Res 2017; 35:785-92.
24 Boyd SK, Muller R, Zernicke RF. Mechanical and architectural bone adaptation in early stage experimental osteoarthritis. J Bone Miner Res 2002; 17:687-94.
25 Frost HM. From Wolff's law to the Utah paradigm: insights about bone physiology and its clinical applications. Anat Rec 2001; 262:398-419.
26 Matsui H, Shimizu M, Tsuji H. Cartilage and subchondral bone interaction in osteoarthrosis of human knee joint: a histological and histomorphometric study. Microsc Res Tech 1997; 37:333-42.
27 Nakasa T, Ishikawa M, Takada T, Miyaki S, Ochi M. Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice. J Orthop Res 2016; 34:1177-84.
28 Zhu XB, Chan YT, Yung PSH, Tuan RS, Jiang Y. Subchondral bone remodeling: a therapeutic target for osteoarthritis. Front Cell Dev Biol 2020; 8:607764.
29 Xu B, Xing RL, Huang ZQ, et al. Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model. Life Sci 2019; 228:158-66.
30 He ZN, Nie PF, Lu JL, et al. Less mechanical loading attenuates osteoarthritis by reducing cartilage degeneration, subchondral bone remodelling, secondary inflammation, and activation of NLRP3 inflammasome. Bone Joint Res 2020; 9:731-41.
31 Wu L, Guo HH, Sun KN, Zhao X, Ma T, Jin CH. Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. Int J Mol Med 2016; 38:1395-402.
32 Cui Z, Crane J, Xie H, et al. Halofuginone attenuates osteoarthritis by inhibition of TGF-beta activity and H-type vessel formation in subchondral bone. Ann Rheum Dis 2016; 75:1714-21.
33 Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019; 27:1578-89.
34 Arden NK, Perry TA, Bannuru RR, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol 2021; 17:59-66.
35 Greif DN, Emerson CP, Jose J, Toumi H, Best TM. Enthesopathy-an underappreciated role in osteoarthritis? Curr Sports Med Rep 2020; 19:495-7.
36 Resorlu M, Doner D, Karatag O, Toprak CA. The Relationship between chondromalacia patella, medial meniscal tear and medial periarticular bursitis in patients with osteoarthritis. Radiol Oncol 2017; 51:401-6.
37 Zhong WQ, Lao JX, Li SC, et al. Observation on the difference of curative effect between Neixiyan and Waixiyan on degenerative knee osteoarthritis. Guang Ming Zhong Yi 2011; 26:108-9.
38 Que Q H, He F, Wang J, et al. Application of five points behind the knee combined with electroacupuncture in the treatment of early knee osteoarthritis. Rehabilitation Medicine 2014; 24:55-6.
39 Zhang TM, Zhang Q, Zeng CX, et al. The tool and effect principle of acupotomology. Zhong Guo Yi Yao Dao Bao 2016; 13:163-6.
40 Liu BZ. Study on the etiology and pathology of chronic soft tissue injury and the mechanism of acupotomy. Zhong Guo Zhong Yi Yao Xian Dai Yuan Chen Jiao Yu 2012; 10:58-60.
41 Lin WC, Liu CY, Tang CL, Hsu CH. Acupuncture and small needle scalpel therapy in the treatment of calcifying tendonitis of the gluteus medius: a case report. Acupunct Med 2012; 30.
42 Mills K, Hunt MA, Leigh R, Ferber R. A systematic review and Meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking. Clin Biomech (Bristol, Avon) 2013; 28:713-24.
43 Fu D E L, Guo CQ, Jin XF, et al. Effect of acupotomy treatment on tensile mechanical properties of medial collateral ligaments in a rabbit model of knee osteoarthritis. Shi Jie Zhong Yi Yao 2014; 9:912-5.
44 Wang LJ, Shi XW, Zhang W, Wang T, Zhou S, Guo CQ. Effect of needle knife intervention on tensile mechanics of femoral quadriceps tendon in rabbits with knee osteoarthritis. Zhong Guo Gu Shang 2019; 32:462-8.
45 Hu B, Yu JN, Zhang HF, Liu NG, Guo CQ. Effect of acupotomy intervention on contractility of quadriceps femoris and pathological changes of articular cartilage in KOA rabbits. Zhen Jiu Lin Chuang Za Zhi 2018; 34:50-4.
46 Gao Y, Wang T, Zhang W, et al. Effect of acupotomy on chondrocyte proliferation and expression of CyclinD1, CDK4 and CDK6 in rabbits with knee osteoarthritis. J Tradit Chin Med Sci 2019; 6:277-91.
47 Schaffler MB, Kennedy OD. Osteocyte signaling in bone. Curr Osteoporos Rep 2012; 10:118-25.
48 Zheng WW, Li XL, Liu DQ, et al. Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy. Faseb J 2019; 33:4077-88.
49 Zhen G, Wen C, Jia X, et al. Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 2013; 19:704-12.
50 Lin CX, Liu LL, Zeng C, et al. Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12. Bone Res 2019; 7:5.
51 Yang PF, Nie XT, Zhao DD, et al. Deformation regimes of collagen fibrils in cortical bone revealed by in situ morphology and elastic modulus observations under mechanical loading. J Mech Behav Biomed Mater 2018; 79:115-21.
52 Garnero P. The role of collagen organization on the properties of bone. Calcif Tissue Int 2015; 97:229-40.
53 Bailey AJ, Sims TJ, Knott L. Phenotypic expression of osteoblast collagen in osteoarthritic bone: production of type I homotrimer. Int J Biochem Cell Biol 2002; 34:176-82.
54 Zhang Y, Paul EM, Sathyendra V, et al. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One 2011; 6:e23516.
55 Sanchez C, Pesesse L, Gabay O, et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression. Arthritis Rheum 2012; 64:1193-203.
56 Chatmahamongkol C, Pravitharangul A, Suttapreyasri S, Leethanakul C. The effect of compressive force combined with mechanical vibration on human alveolar bone osteoblasts. J Oral Biol Craniofac Res 2019; 9:81-5.
57 Wu YQ, Zhang P, Dai QG, et al. Osteoclastogenesis accom-panying early osteoblastic differentiation of BMSCs promoted by mechanical stretch. Biomed Rep 2013; 1:474-8.
58 Vaysbrot EE, Osani MC, Musetti MC, McAlindon TE, Bannuru RR. Are bisphosphonates efficacious in knee osteoarthritis? A Meta-analysis of randomized controlled trials. Osteoarthritis Cartilage 2018; 26:154-64.
59 Martel-Pelletier J, Barr AJ, Cicuttini FM, et al. Osteoarthritis. Nat Rev Dis Primers 2016; 2:16072.
60 Sun YJ, Wu YC, Zhang FJ, Zhang P, Tang ZY. Effects of electroacupuncture on muscle state and electrophysiological changes in rabbits with lumbar nerve root compression. Chin J Integr Med 2013; 19:446-52.
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