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      Shockwave Targeting on Subchondral Bone Is More Suitable than Articular Cartilage for Knee Osteoarthritis

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          Abstract

          Our study compared the effects of extracorporeal shockwave therapy (ESWT) on the subchondral bone and the articular cartilage in the treatment of early osteoarthritis (OA) of rat knee. The rats were divided into 5 groups which included Sham group, Meniscus group (ESWT applied on medial meniscus), OA group (arthrotomy and medial menisectomy (MMx) and anterior cruciate ligament transection (ACLT), T(M) group (arthrotomy and MMx and ACLT followed by ESWT on medial tibial subchondral bone) and Articular cartilage group (arthrotomy and MMx and ACLT followed by ESWT on medial articular cartilage). Evaluations included the pathological changes of the synovium, articular cartilage and subchondral bone, and compared with ESWT on the meniscus, medial tibial subchondral bone and articular cartilage. The ESWT (0.25 mJ/mm ² and 800 impulses) did not cause any damages on the cartilage of the meniscus and the tissue of the joint when compared with Sham group. Among the treatment of osteoarthritic groups (OA, T(M) and Articular cartilage groups), T(M) group showed significant in pathological examination, micro-CT analysis, cartilage grading score and grading of synovium changes by compared with OA and Articular cartilage groups ( P < 0.05) in the treatment of early OA knee. In immunohistochemical analysis, T(M) group significantly increased the expression of TGF-β1 but reduced DMP-1, MMP-13 and ADAMTS-5 in the cartilage by compared with OA group and Articular cartilage group ( P < 0.05). Our results showed that subchondral bone was an excellent target than articular cartilage for ESWT on early knee osteoarthritis.

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          Most cited references42

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          Synovitis score: discrimination between chronic low-grade and high-grade synovitis.

          To standardize the histopathological assessment of synovial membrane specimens in order to contribute to the diagnostics of rheumatic and non-rheumatic joint diseases. Three features of chronic synovitis (enlargement of lining cell layer, cellular density of synovial stroma, leukocytic infiltrate) were semiquantitatively evaluated (from 0, absent to 3, strong) and each feature was graded separately. The sum provided the synovitis score, which was interpreted as follows: 0-1, no synovitis; 2-4, low-grade synovitis; 5-9, high-grade synovitis. Five hundred and fifty-nine synovectomy specimens were graded by two independent observers. Clinical diagnoses were osteoarthrosis (n=212), post-traumatic arthritis (n=21), rheumatoid arthritis (n=246), psoriatic arthritis (n=22), reactive arthritis (n=9), as well as controls (n=49) from autopsies of patients without joint damage. Median synovitis scores when correlated with clinical diagnoses were: controls 1.0, osteoarthritis 2.0, post-traumatic arthritis 2.0, psoriatic arthritis 3.5, reactive arthritis 5.0 and rheumatoid arthritis 5.0. The scores differed significantly between most disease groups, especially between degenerative and rheumatic diseases. A high-grade synovitis was strongly associated with rheumatic joint diseases (P<0.001, sensitivity 61.7%, specificity 96.1%). The correlation between the two observers was high (r=0.941). The proposed synovitis score is based on well-defined, reproducible histopathological criteria and may contribute to diagnosis in rheumatic and non-rheumatic joint diseases.
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            Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

            Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.
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              Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition.

              Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline, 2nd Edition, is based on a systematic review of the current scientific and clinical research. This guideline contains 15 recommendations, replaces the 2008 AAOS clinical practice guideline, and was reevaluated earlier than the 5-year recommendation of the National Guideline Clearinghouse because of methodologic concerns regarding the evidence used in the first guideline. The current guideline does not support the use of viscosupplementation for the treatment of osteoarthritis of the knee. In addition, the work group highlighted the need for better research in the treatment of knee osteoarthritis.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2019
                1 January 2019
                : 16
                : 1
                : 156-166
                Affiliations
                [1 ]Section of Sports Medicine, Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
                [2 ]Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
                [3 ]Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
                Author notes
                ✉ Corresponding authors: Ching-Jen Wang, M. D. Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Tai-Pei Road, Niao Sung District, Kaohsiung, Taiwan 833. Tel.: 886-7-733-5279; Fax: 886-7-733-5515; Email: w281211@ 123456adm.cgmh.org.tw or Jai-Hong Cheng, Ph. D. Center for Shockwave Medicine and Tissue Engineering, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123 Tai-Pei Road, Niao Sung District, Kaohsiung, Taiwan 833. Fax: +886-7-7317123 ext 8150. Tel: +886-7-731-7123 ext 6422. E-mail address: jh1106520@ 123456gmail.com

                Competing interests: The authors declared that they did not receive any honoraria or consultancy fees in writing this manuscript. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. One author (CJW) serves as a member of the advisory committee of SANUWAVE Health, Inc. (Suwanee, GA) and this study is performed independent of the appointment. The remaining authors declared no conflict of interest.

                Article
                ijmsv16p0156
                10.7150/ijms.26659
                6332487
                30662339
                f11bf023-beec-41fc-8f7e-778bb40fc8bd
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 13 April 2018
                : 29 November 2018
                Categories
                Research Paper

                Medicine
                extracorporeal shock wave therapy,osteoarthritis,articular cartilage,knee,tissue regeneration

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