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      Effects of platelet-rich plasma combined with isometric quadriceps contraction on cartilage in a rat model of knee osteoarthritis

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          Abstract

          Background

          Intra-articular injection of platelet-rich plasma (PRP) or isometric contraction of quadriceps (ICQ) has shown positive effects in patients with knee osteoarthritis (KOA). However, the synergistic effect of combining PRP and ICQ intervention (joint intervention) on cartilage repair has not been validated. Thus, this study aimed to explore the reparative effects of joint intervention on cartilage in a KOA rat model.

          Methods

          Fifty-four 2-month-old female Sprague-Dawley rats were randomly divided into the control group (CG, n = 6) and model group (injected with sodium iodoacetate, n = 48). After 1 week, six rats from the model group were randomly selected for validation. The remaining 42 rats were further divided into seven groups: PRP group (PRPG), ICQ group (ICQG), joint intervention group (JIG), normal saline group (NSG), acupuncture group (AG), normal saline and acupuncture group (NSAG) and model blank group (MBG). The intervention lasted for 4 weeks, with PRPG and JIG receiving PRP injections (twice) and ICQG and JIG undergoing ICQ (five times per week, 15 min each session).

          Results

          Histological staining with haematoxylin and eosin as well as transmission electron microscopy revealed severe cartilage damage in MBG, AG, NSAG and NSG, followed by PRPG and ICQG. JIG exhibited a more intact cartilage structure. Compared with JIG, the Mankin scores increased remarkably in PRPG, ICQG, AG, NSAG and NSG ( P < 0.01). Relative mRNA expression levels showed the upregulation of IL-1β in ICQG, NSAG and NSG compared with JIG ( P < 0.05) and the upregulation of IL-6, IL-18 and MMP-13 in AG and NSAG ( P < 0.05). Compared with PRPG, IL-1β and IL-6 were upregulated in ICQG, AG, NSAG and NSG ( P < 0.05). In addition, IL-18 was upregulated in AG ( P < 0.01), and IL-18, MMP-13 and TNF-α were upregulated in NSAG ( P < 0.05). Compared with ICQG, IL-1β, IL-18, MMP-13 and TNF-α were upregulated in NSAG ( P < 0.05), and IL-1β and IL-18 were upregulated in AG ( P < 0.05).

          Conclusion

          The combination of PRP and ICQ can alleviate inflammatory responses in cartilage, promote chondrocyte regeneration and facilitate matrix tissue repair. Compared with single interventions, a synergistic effect is observed.

          Highlights

          • Platelet-rich plasma and isometric contraction of quadriceps can promote the regeneration of chondrocytes, and repair matrix tissue.

          • Compared to single interventions, the combined intervention is more effective for knee osteoarthritis.

          • Combined intervention play a better role in reducing inflammation, promoting cartilage repair of interaction.

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          Most cited references62

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          The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

          Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.
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            Osteoarthritis of the Knee

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              The CH25H–CYP7B1–RORα axis of cholesterol metabolism regulates osteoarthritis

              Osteoarthritis-the most common form of age-related degenerative whole-joint disease1-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated4-6. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes7,8. Here we show that the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (RORα) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-RORα axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.
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                Author and article information

                Contributors
                Journal
                Regen Ther
                Regen Ther
                Regenerative Therapy
                Japanese Society for Regenerative Medicine
                2352-3204
                15 July 2024
                June 2024
                15 July 2024
                : 26
                : 469-477
                Affiliations
                [a ]School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China
                [b ]Sichuan Academy of Chinese Medicine Sciences, Chengdu, China
                [c ]Human Movement Science, Sichuan Sports College, Chengdu, China
                [d ]Affiliated Sport Hospital of Chengdu Sport University, Chengdu, China
                Author notes
                [* ]Corresponding author. 1131389799@ 123456qq.com
                [** ]Corresponding author. BenxiangHe@ 123456163.com
                Article
                S2352-3204(24)00128-7
                10.1016/j.reth.2024.06.021
                11283084
                39070125
                a596593f-2ad5-410b-9827-dc2b4f2da18e
                © 2024 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 June 2024
                : 23 June 2024
                : 27 June 2024
                Categories
                Original Article

                knee osteoarthritis,platelet-rich plasma,isometric contraction of quadriceps

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