Advanced Search

Journal of Traditional Chinese Medicine >

2023 , Vol. 43 >Issue 4: 734 - 743

DOI: https://doi.org/10.19852/j.cnki.jtcm.20230404.001

Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway

  • Xilin Chen ,
  • Yan GUO ,
  • Juan LU ,
  • Luxue QIN ,
  • Tingyao HU ,
  • Xin ZENG ,
  • Xinyue WANG ,
  • Anran ZHANG ,
  • Yuxin ZHUANG ,
  • Honggang ZHONG ,
  • Changqing GUO
Expand
  • 1 School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China
    2 Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated with Capital Medical University, Beijing 100010, China
    3 Shenzhen Hospital of Southern Medical University, Shenzhen 518000, China
    4 Institute of Bone Injury, China Academy of Chinese Medical Sciences, Beijing 100010, China

Received date: 2022-12-02

  Accepted date: 2023-03-13

  Online published: 2023-04-04

Supported by

Longitudinal Research Development Fund of Beijing University of Chinese Medicine: to Investigate the Effect of Acupotomy on Subchondral Bone Remodeling in Knee Osteoarthritis Based on BMP2-Smad1 Pathway(2020-ZXFZJJ-031);National Natural Science Foundation of China: to Investigate the Mechanism of Acupotomy "Regulating Tendon and Treating Bone" in the Treatment of KOA based on the Vascularization of Hypoxic Cartilage Mediated by HIF-1α/VEGF Pathway(82074523)

Fold

Abstract

OBJECTIVE: To investigate the effects of acupotomy on the subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis (KOA).

METHODS: The rabbits were divided into blank control, model, acupotomy and electroacupuncture (EA) groups, with 12 rabbits in each. Modified Videman’s method was used to prepare KOA model. The acupotomy and EA group were given indicated intervention for 3 weeks. The behavior of rabbits in each group was recorded. Subsequently, cartilage-subchondral bone units were obtained and morphological changes were observed by optical microscope and micro computed tomography. Compression test was used to detect the mechanical properties of subchondral bone, Western blot and real-time polymerase chain reaction (RT-PCR) were applied to detect the expression of bone morphogenetic protein 2-Smad1 (BMP2-Smad1) pathway in subchondral bone.

RESULTS: Compared with the control group, rabbits in the KOA group showed lameness, knee pain, and cartilage degradation; the subchondral bone showed active resorption, the mechanical properties decreased significantly and the BMP2-Smad1 pathway downregulated significantly. Both acupotomy and EA intervention could increase the thickness of trabecular bone (Tb. Th), the bone volume fraction (BV/TV) and the thickness of subchondral bone plate, reduce the separation of trabecular bone (Tb. Sp), improve the maximum load and elastic modulus of subchondral bone, and effectively delay cartilage degeneration in KOA rabbits. This process may be achieved through upregulation the related proteins of BMP2-Smad1 pathway. The maximum load and elastic modulus of subchondral bone in the acupotomy group were slightly better than those in the EA group.

CONCLUSIONS: Acupotomy could effectively protect cartilage by inhibiting abnormal bone resorption and improving mechanical properties of subchondral bone thorough the related proteins of BMP2-Smad1 pathway in KOA rabbits.

Key words： acupuncture therapy; osteoarthritis, knee; subchondral bone; mechanical properties; bone morphogenetic protein 2; Smad1 protein

Cite this article

Xilin Chen , Yan GUO , Juan LU , Luxue QIN , Tingyao HU , Xin ZENG , Xinyue WANG , Anran ZHANG , Yuxin ZHUANG , Honggang ZHONG , Changqing GUO . Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway[J]. Journal of Traditional Chinese Medicine, 2023 , 43(4) : 734 -743 . DOI: 10.19852/j.cnki.jtcm.20230404.001

References

1. Moore N, Salvo F, Duong M, Gulmez SE. Does paracetamol still have a future in osteoarthritis? Lancet 2016; 387: 2065-66.
2. Hu W, Chen Y, Dou C, Dong S. Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis. Ann Rheum Dis 2020: 80: 413-22.
3. Felson DT. Osteoarthritis as a disease of mechanics. Osteoarthritis Cartilage 2013; 21: 10-5.
4. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol 2012; 8: 665-73.
5. Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep 2014; 3: 481.
6. Bei MJ, Tian FM, Xiao YP, et al. Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced- patellofemoral joint osteoarthritis. Osteoarthritis Cartilage 2020; 28: 344-55.
7. Hayes KN, Giannakeas V, Wong A. Bisphosphonate use is protective of radiographic knee osteoarthritis progression among those with low disease severity and being non-overweight: data from the osteoarthritis initiative. J Bone Miner Res 2020; 35: 2318-26.
8. Zhu D, Deng X, Han XF, et al. Wedelolactone enhances osteoblastogenesis through ERK- and JNK-mediated BMP2 expression and Smad/1/5/8 phosphorylation. Molecules 2018; 23: 561.
9. Iijima H, Ito A, Nagai M, et al. Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model. Osteoarthr Cartilage 2016; 25: 964-75.
10. Guo CQ, Si T, Wen JM, et al. A randomized controlled clinical study on the improvement of pain symptoms of knee osteoarthritis with acupotomy. Tianjin Zhong Yi Yao 2012; 29: 35-8.
11. Wu YEED, Guo CQ, Wang T, et al. Effect of acupotomy on extensor - flexor atrophy and elastic modulus of muscle tension in rabbit model of mid - stage knee osteoarthritis. Hunan Zhong Yi Yao Da Xue Xue Bao 2019; 39: 1248-53.
12. 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.
13. Frost HM. Wolff's Law and bone's structural adaptations to mechanical usage: an overview for clinicians. Angle Orthod 1994; 64: 175-88.
14. Hugle T, Geurts J. What drives osteoarthritis? -synovial versus subchondral bone pathology. Rheumatology (Oxford) 2017; 56: 1461-71.
15. Wang T, Guo Y, Shi XW, et al. Acupotomy contributes to suppressing subchondral bone resorption in KOA rabbits by regulating the OPG/RANKL signaling pathway. Evid Based Complement Alternat Med 2021; 2021: 8168657.
16. Videman T. Experimental osteoarthritis in the rabbit: comparison of different periods of repeated immobilization. Acta Orthop Scand 1982; 53: 339-47.
17. Lequesne MG, Mery C, Samson M, et al. Indexes of severity for osteoarthritis of the hip and knee. Validation--value in comparison with other assessment tests. Scand J Rheumatol 1988; 17: 241.
18. Guo CQ. Acupotomology. Beijing: China Press of Traditional Chinese Medicine, 2017: 199-204.
19. Li ZR. Experimental acupuncture science. Beijing: China Press of Traditional Chinese Medicine, 2007: 314-30.
20. 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.
21. Felson DT. Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 2009; 11: 203.
22. O'Neill TW, Felson DT. Mechanisms of osteoarthritis (OA) pain. Curr Osteoporos Rep 2018; 16: 611-6.
23. Zaki S, Blaker CL, Little CB. OA foundations-experimental models of osteoarthritis. Osteoarthritis Cartilage 2022; 30: 357-80.
24. Christiansen BA, Guilak F, Lockwood KA, et al. Non-invasive mouse models of post-traumatic osteoarthritis. Osteoarthritis Cartilage 2015; 23: 1627-38.
25. Kikuchi T, Sakuta T, Yamaguchi T. Intra-articular injection of collagenase induces experimental osteoarthritis in mature rabbits. Osteoarthritis Cartilage 1998; 6: 177-86.
26. Beuningen HM, Glansbeek HL, Kraan PM, Berg WB. Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor-beta injections. Osteoarthritis Cartilage 2000; 8: 25-33.
27. Shi X, Yu W, Wang T, et al. Electroacupuncture alleviates cartilage degradation: improvement in cartilage biomechanics via pain relief and potentiation of muscle function in a rabbit model of knee osteoarthritis. Biomed Pharmacother 2020; 123: 109724.
28. Takagi S, Omori G, Koga H, et al. Quadriceps muscle weakness is related to increased risk of radiographic knee OA but not its progression in both women and men: the Matsudai knee osteoarthritis survey. Knee Surg Sports Traumatol Arthrosc 2018; 26: 2607-14.
29. Stewart HL, Kawcak CE. The importance of subchondral bone in the pathophysiology of osteoarthritis. Front Vet Sci 2018; 5: 178.
30. Norrdin RW, Kawcak CE, Capwell BA, McIlwraith CW. Subchondral bone failure in an equine model of overload arthrosis. Bone 1998; 22: 133-9.
31. McIlwraith CW, Frisbie DD, Kawcak CE, Weeren RV. Joint disease in the horse. Saunders: Saunders/Elsevier, 2016: 408.
32. Kawcak CE, McIlwraith CW, Norrdin RW, Park RD, James SP. The role of subchondral bone in joint disease: a review. Equine Vet J 2001; 33: 120-6.
33. Cabahug-Zuckerman P, Frikha-Benayed D, Majeska RJ, et al. Osteocyte apoptosis caused by hindlimb unloading is required to trigger osteocyte RANKL production and subsequent resorption of cortical and trabecular bone in mice femurs. J Bone Miner Res 2016; 31: 1356-65.
34. Li B, Aspden RM. Mechanical and material properties of the subchondral bone plate from the femoral head of patients with osteoarthritis or osteoporosis. Ann Rheum Dis 1997; 56: 247-54.
35. Hernandez CJ, Lambers FM, Widjaja J, Chapa C, Rimnac CM. Quantitative relationships between microdamage and cancellous bone strength and stiffness. Bone 2014; 66: 205-13.
36. He Z, Chu L, Liu X, et al. Differences in subchondral trabecular bone microstructure and finite element analysis-based biomechanical properties between osteoporosis and osteoarthritis. J Orthop Translat 2020; 24: 39-45.
37. Lampropoulou-Adamidou K, Dontas I, Stathopoulos IP, et al. Chondroprotective effect of high-dose zoledronic acid: an experimental study in a rabbit model of osteoarthritis. J Orthop Res 2014; 32: 1646-51.
38. Miao X, Yuan J, Wu J, et al. Bone morphogenetic protein-2 promotes osteoclasts-mediated osteolysis via Smad1 and p65 signaling pathways. Spine (Phila Pa 1976) 2021; 46: E234-42.
39. Tao ZS, Zhou WS, Xu HG, Yang M. Aspirin modified strontium-doped beta-tricalcium phosphate can accelerate the healing of femoral metaphyseal defects in ovariectomized rats. Biomed Pharmacother 2020; 132: 110911.
40. Blaney DE, Vitters EL, Lent PL, Loo FA, Berg WB, Kraan PM. Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodeling. Arthritis Res Ther 2007; 9: R102.
41. Simic P, Culej JB, Orlic I, et al. Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J Biol Chem 2006; 281: 25509-21.
42. Betz VM, Keller A, Foehr P, et al. BMP-2 gene activated muscle tissue fragments for osteochondral defect regeneration in the rabbit knee. J Gene Med 2017; 19: 9-10.
43. An X, Wang T, Zhang W, et al. Chondroprotective effects of combination therapy of acupotomy and human adipose mesenchymal stem cells in knee osteoarthritis rabbits via the GSK3β-Cyclin D1-CDK4/CDK6 signaling pathway. Aging Dis 2020; 11: 1116-32.
44. Qin LX, Guo CQ, Zhao RL, et al. 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 Tradit Chin Med 2022; 42: 389-99.
45. Fernandez-Martin S, Lopez-Pena M, Munoz F, Permuy M, Gonzalez-Cantalapiedra A. Bisphosphonates as disease-modifying drugs in osteoarthritis preclinical studies: a systematic review from 2000 to 2020. Arthritis Res Ther 2021; 23: 60.
46. McGrory B, Weber K, Lynott JA, et al. The American Academy of orthopaedic surgeons evidence-based clinical practice guideline on surgical management of osteoarthritis of the knee. J Bone Joint Surg Am 2016; 98: 688-92.
47. Tan Q, Cai Z, Li J, et al. Imaging study on acupuncture inhibiting inflammation and bone destruction in knee osteoarthritis induced by monosodium iodoacetate in rat model. J Pain Res 2022; 15: 93-103.
Options
Outlines

/

〈 〉