Early-stage knee OA induced by MIA and MMT compared in the murine model via histological and topographical approaches

Aüllo-Rasser, Gaëtan; Dousset, Erick; Roffino, Sandrine; Zahouani, H.; Lecurieux-Clerville, Roger; Argenson, Jean-Noël; Chabrand, Patrick

doi:10.1038/s41598-020-72350-7

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…Previous studies of the collagenous network in human knee joints have found that OA progression results in collagenous disorganization of the posterior meniscal horn 21 and misaligned, thickened fibers in the superficial and deep zones of the articular cartilage 31 , which contribute to structural changes leading to tissue degradation. Our study extends the scope of previous studies that focused on examining the initial changes that occur in the cartilage during early OA 4 , 16 , 32 , or singular joint tissues 21 . Here, we define regional differences in the medial compartment of the knee in late OA, which provides indication of how load is being re-distributed in later stages of the disease.…”

Section: Discussionsupporting

confidence: 63%

“…Osteoarthritis (OA) is the most prevalent degenerative joint disease and is characterized by limited mobility and impaired joint function. The ability of joints to withstand stress is affected by factors such as age, injury, obesity, and genetics, which can predispose individuals to develop OA 1 – 4 . Although OA has been initially classified as a disease of articular cartilage degeneration, recent studies have demonstrated the impact of OA on other joint tissues.…”

Section: Introductionmentioning

confidence: 99%

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Structural changes in the collagen network of joint tissues in late stages of murine OA

Yoshioka

Young

Khajuria

et al. 2022

Sci Rep

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Osteoarthritis (OA) is the most prevalent degenerative joint disease, resulting in joint pain, impaired movement, and structural changes. As the ability of joint tissue to resist stress is mainly imparted by fibrillar collagens in the extracellular matrix, changes in the composition and structure of collagen fibers contribute to the pathological remodeling observed in OA joints that includes cartilage degeneration, subchondral bone (SCB) sclerosis, and meniscal damage. Using the established OA model of destabilization of the medial meniscus (DMM) in C57BL/6J mice, we performed a comprehensive analysis of the content and structure of collagen fibers in the articular cartilage, subchondral bone, and menisci using complementary techniques, which included second harmonic generation microscopy and immunofluorescence staining. We found that regions exposed to increased mechanical stress in OA mice, typically closest to the site of injury, had increased collagen fiber thickness, dysregulated fiber formation, and tissue specific changes in collagen I and II (Col I and Col II) expression. In cartilage, OA was associated with decreased Col II expression in all regions, and increased Col I expression in the anterior and posterior regions. Col I fiber thickness was increased in all regions with disorganization in the center region. In the superficial SCB, all regions exhibited increased Col I expression and fiber thickness in OA mice; no changes were detected in the deeper regions of the subchondral bone except for increased Col I fiber thickness. In the menisci, OA led to increased Col I and Col II expression in the vascular and avascular regions of the anterior meniscus with increased Col I fiber thickness in these regions. Similar changes were observed only in the vascular region of the posterior meniscus. Our findings provide, for the first time, comprehensive insights into the microarchitectural changes of extracellular matrix in OA and serve as guidelines for studies investigating therapies that target collagenous changes as means to impede the progression of osteoarthritis.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Structural changes in the collagen network of joint tissues in late stages of murine OA

Yoshioka

Young

Khajuria

et al. 2022

Sci Rep

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“…Gait analysis was completed by evaluating footprints made by inking the back paws. While for all groups the average measurements of gait were relatively low (< 1, normal = 0), this was expected due to the mild nature of the MMT model compared to others [ 21 ]. The 50 μL ASA group had a significantly lower gait score compared to the vehicle control at 9 days ( p < 0.05; Fig.…”

Section: Resultsmentioning

confidence: 99%

Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model

et al. 2022

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Background Osteoarthritis is a degenerative disease of the knee that affects 250 million people worldwide. Due to the rising incidence of knee replacement and revision surgery, there is a need for a nonsurgical treatment to reduce pain and improve function in patients with knee osteoarthritis. Placental-derived allografts, such as an amniotic suspension allograft (ASA), provide growth factors and cytokines that could potentially modulate the inflammatory environment of osteoarthritis. The purpose of this study was to evaluate the efficacy of ASA in a rat medial meniscal tear (MMT) induced osteoarthritis model through histology, microCT, synovial fluid biomarkers, and behavioral testing. Methods Rats underwent MMT surgery at day − 7; at day 0, rats were injected with either ASA, vehicle control, or fibroblast growth factor-18 (FGF18). Behavioral testing, including gait analysis, pain threshold, incapacitance, and knee swelling were evaluated in-life, along with histology, microCT analysis of cartilage, and synovial fluid testing post-sacrifice. One MMT cohort was sacrificed at day 10, the other at day 21. A third cohort acted as a safety arm and did not receive MMT surgery; these rats were injected with either vehicle control or ASA and evaluated at day 3 and day 21. Results Behavioral testing showed a significant improvement in pain threshold, incapacitance, and gait following an injection of ASA. MicroCT showed significant improvements in cartilage thickness and attenuation at day 10 only, and histology showed no detrimental effects compared to the vehicle control at day 21. Synovial fluid analysis showed a significant increase in anti-inflammatory IL-10. The safety cohort showed no significant differences except for an increase in synovitis at day 21, which could be evidence of a xenogeneic response in this model. Conclusions In this study, an injection of ASA was well tolerated with no adverse events. Improvements in pain and function, along with cartilage properties at day 10, were observed. Increases in anti-inflammatory cytokines was also seen, along with no significant cartilage degeneration at day 21 compared to the vehicle control. This study provides evidence for the use of ASA as a nonsurgical treatment for knee OA.

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“…The Nanjing Medical University Animal Center (Nanjing, China) provided male adult Sprague–Dawley (SD) rats (2 months, n = 24) and were randomly assigned to the sham, MMT, MMT + GSK101, or MMT + HC067047 groups. Following one week of adaptive feeding, 18 rats underwent a medial meniscus radial transection operation to create an OA model [ 20 ]. Six rats underwent a sham operation.…”

Section: Methodsmentioning

confidence: 99%

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

Sun

et al. 2022

Antioxidants

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Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.

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Early-stage knee OA induced by MIA and MMT compared in the murine model via histological and topographical approaches

Cited by 11 publications

References 26 publications

Structural changes in the collagen network of joint tissues in late stages of murine OA

Structural changes in the collagen network of joint tissues in late stages of murine OA

Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

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