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      Oral shea nut oil triterpene concentrate supplement ameliorates pain and histological assessment of articular cartilage deterioration in an ACLT injured rat knee osteoarthritis model

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      PLoS ONE
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          Abstract

          Osteoarthritis (OA) is a multifactorial joint disease and a common disabling condition in the elderly population. The associated pain and pathohistological changes in cartilage are common features of OA in both humans and animal models. Shea nut oil extract (SheaFlex75) contains a high triterpenoid concentration and has demonstrated anti-inflammatory and antiarthritic effects in both human and animal studies. In this study, we aim to investigate the potential of SheaFlex75 to prevent articular cartilage deterioration in a rat model of chronic OA progression. By employing anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx)-induced OA, we found attenuation of both early and chronic onset OA pain and cartilage degeneration in ACLT+MMx rats receiving SheaFlex75 dietary supplementation. Under long-term oral administration, the rats with induced OA presented sustained protection of both pain and OA cartilage integrity compared to the OA-control rats. Moreover, rats subjected to long-term SheaFlex75 ingestion showed normal biochemical profiles (AST, BUN and total cholesterol) and presented relatively lower triglycerides (TGs) and body weights than the OA-control rats, which suggested the safety of prolonged use of this oil extract. Based on the present evidence, preventive management is advised to delay/prevent onset and progression in OA patients. Therefore, we suggest that SheaFlex75 may be an effective management strategy for symptom relief and cartilage protection in patients with both acute and chronic OA.

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          Most cited references42

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          Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care.

          Osteoarthritis is the single most common cause of disability in older adults, and most patients with the condition will be managed in the community and primary care. To discuss case definition of knee osteoarthritis for primary care and to summarise the burden of the condition in the community and related use of primary health care in the United Kingdom. Narrative review. A literature search identified studies of incidence and prevalence of knee pain, disability, and radiographic osteoarthritis in the general population, and data related to primary care consultations. Findings from UK studies were summarised with reference to European and international studies. During a one year period 25% of people over 55 years have a persistent episode of knee pain, of whom about one in six in the UK and the Netherlands consult their general practitioner about it in the same time period. The prevalence of painful disabling knee osteoarthritis in people over 55 years is 10%, of whom one quarter are severely disabled. Knee osteoarthritis sufficiently severe to consider joint replacement represents a minority of all knee pain and disability suffered by older people. Healthcare provision in primary care needs to focus on this broader group to impact on community levels of pain and disability.
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            The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat.

            During the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigators. The experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring. Considerations were made for reproducibility and ease of use for new scorers. Additional scoring paradigms may be employed to further identify specific effects of some disease-modifying drugs. Although the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the reliability study showed that it is easily understood and can be reproducibly used, even by inexperienced scorers. The scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility. Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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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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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Formal analysis
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 April 2019
                2019
                : 14
                : 4
                : e0215812
                Affiliations
                [1 ] Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
                [2 ] Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
                [3 ] Planing and Management Office, Tri-Service General Hospital, Taipei, Taiwan
                [4 ] Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
                Ain Shams University, EGYPT
                Author notes

                Competing Interests: The authors were contracted by Universal Integrated Corp., a commercial company located in Taipei, Taiwan, to study the effect of the product SheaFlex75 on their well-established OA animal model, ACLT plus MMx. Additionally, neither we nor any of our team members received any extra financial support outside of that stated in the Financial Disclosure, and none of our research team members are company consultants or own patents and benefits from the product’s sales. There are no products in development to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0003-3951-129X
                http://orcid.org/0000-0001-9898-9950
                Article
                PONE-D-18-23308
                10.1371/journal.pone.0215812
                6474620
                31002699
                a76c7b18-32cf-47b1-be77-489e1846e5ab
                © 2019 Chen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 August 2018
                : 9 April 2019
                Page count
                Figures: 5, Tables: 1, Pages: 15
                Funding
                This study received financial support in the form of a contract from Universal Integrated Corp., Taipei, Taiwan, a commercial company. Universal Integrated Corp. was not involved in any part of the study design or conduct, data collection or data analysis, or manuscript writing.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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