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  • 1
    Online Resource
    Online Resource
    Intra‐articular injection of triamcinolone acetonide sustains macrophage levels and aggravates osteophytosis during degenerative joint disease in mice
    Wiley ; 2022
    In:  British Journal of Pharmacology Vol. 179, No. 11 ( 2022-06), p. 2771-2784
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 179, No. 11 ( 2022-06), p. 2771-2784
    Abstract: Corticosteroids such as triamcinolone acetonide (TAA) are potent drugs administered intra‐articularly as an anti‐inflammatory therapy to relieve pain associated with osteoarthritis (OA). However, the ability of early TAA intervention to mitigate OA progression and modulate immune cell subsets remains unclear. Here, we sought to understand the effect of early intra‐articular injection of TAA on OA progression, local macrophages, and peripheral blood monocytes. Experimental approach Degenerative joint disease was induced by intra‐articular injection of collagenase into the knee joint of male C57BL/6 mice. After 1 week, TAA or saline was injected intra‐articularly. Blood was taken throughout the study to analyse monocyte subsets. Mice were killed at days 14 and 56 post‐induction of collagenase‐induced OA (CiOA) to examine synovial macrophages and structural OA features. Key results The percentage of macrophages relative to total live cells present within knee joints was increased in collagenase‐ compared with saline‐injected knees at day 14 and was not altered by TAA treatment. However, at day 56, post‐induction of CiOA, TAA‐treated knees had increased levels of macrophages compared with the knees of untreated CiOA‐mice. The distribution of monocyte subsets present in peripheral blood was not altered by TAA treatment during the development of CiOA. Osteophyte maturation was increased in TAA‐injected knees at day 56. Conclusion and implications Intra‐articular injection of TAA increases long‐term synovial macrophage numbers and osteophytosis. Our findings suggest that TAA accentuates the progression of osteoarthritis‐associated features when applied to an acutely inflamed knee.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    URL: Article
    DOI: 10.1111/bph.v179.11
    DOI: 10.1111/bph.15780
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Chondroprotective Actions of Selective COX-2 Inhibitors In Vivo: A Systematic Review
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 18 ( 2020-09-22), p. 6962-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 18 ( 2020-09-22), p. 6962-
    Abstract: Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21186962
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 3
    Online Resource
    Online Resource
    Meniscal extrusion and degeneration during the course of osteoarthritis in the Murine collagenase‐induced osteoarthritis model
    Wiley ; 2018
    In:  Journal of Orthopaedic Research Vol. 36, No. 9 ( 2018-09), p. 2416-2420
    Details
    In: Journal of Orthopaedic Research, Wiley, Vol. 36, No. 9 ( 2018-09), p. 2416-2420
    Abstract: Meniscal damage is, despite its major role in knee osteoarthritis (OA), often neglected in OA animal models. We evaluated structural meniscal degeneration during the course of OA in the murine collagenase‐induced OA (CIOA) model. To investigate this, OA was induced in the knee joints of 33 male C57BL/6 mice by an intra‐articular injection of 10U collagenase. The mice were sacrificed after 1, 3, 7, 14, 28, and 56 days, and the knees were harvested and processed for histological analysis. As control, six knees were obtained from 16‐week‐old mice in which no OA was induced. Meniscal damage, meniscal extrusion, and articular cartilage damage were evaluated on thionin‐stained sections. Associations between parameters of interest were evaluated with Spearman rho correlation tests. When compared to non‐OA knees, meniscal extrusion was visible from day 1 onwards and meniscal degeneration had a tendency to increase over time. The meniscus damage appeared around the same time as articular cartilage damage (day 14–28) and was statistically significantly more pronounced anterior than posterior, and no differences were seen between medial and lateral menisci. Meniscus and articular cartilage damage were moderately associated in the CIOA knees ( ρ  = 0.57; 95%CI [0.23–0.78]). Our findings suggest that the CIOA model is a valuable model to study the role of meniscal damage during OA progression and can support the development of future preventative treatment strategies. © 2018 The Authors. Journal of Orthopaedic Research ® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2416–2420, 2018.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    URL: Issue
    URL: Article
    DOI: 10.1002/jorr.v36.9
    DOI: 10.1002/jor.23909
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2050452-4
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  • 4
    Online Resource
    Online Resource
    Lack of high BMI-related features in adipocytes and inflammatory cells in the infrapatellar fat pad (IFP)
    Springer Science and Business Media LLC ; 2017
    In:  Arthritis Research & Therapy Vol. 19, No. 1 ( 2017-12)
    Details
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1478-6362
    URL: Article
    DOI: 10.1186/s13075-017-1395-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2041668-4
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  • 5
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    Online Resource
    Macrophage phenotypes and monocyte subsets after destabilization of the medial meniscus in mice
    Wiley ; 2021
    In:  Journal of Orthopaedic Research Vol. 39, No. 10 ( 2021-10), p. 2270-2280
    Details
    In: Journal of Orthopaedic Research, Wiley, Vol. 39, No. 10 ( 2021-10), p. 2270-2280
    Abstract: Macrophages play an important role in the development and progression of osteoarthritis (OA). The aim of this study was to identify macrophage phenotypes in synovium and monocyte subsets in peripheral blood in C57BL/6 mice by destabilizing the medial meniscus (DMM), and the association of macrophage subsets with OA features. DMM, sham, and non‐operated knees were histologically assessed between 1 and 56 days for macrophage polarization states by immunohistochemistry (IHC), cartilage damage, synovial thickening, and osteophytes ( n  = 9 per timepoint). Naive knees ( n  = 6) were used as controls. Monocyte and polarized synovial macrophage subsets were evaluated by flow cytometry. CD64 and CD206 levels on IHC were higher at early timepoints in DMM and sham knees compared to naive knees. iNOS labeling intensity was higher in DMM and sham knees than in naive knees from d3 onwards. CD163 expression was unaltered at all timepoints. Even though macrophage polarization profiles were similar in DMM and sham knees, only in DMM knees the presence of iNOS and CD206 associated with synovial thickness, and CD163 staining inversely correlated with osteophyte presence. At day 14, monocyte subset distribution was different in peripheral blood of DMM mice compared with sham mice. In conclusion, monocyte subsets in blood and synovial macrophage phenotypes vary after joint surgery. High levels of iNOS + , CD163 + , and CD206 + cells are found in both destabilized and sham‐operated knees, and coexistence with joint instability may be a requirement to initiate and exacerbate OA progression.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    URL: Issue
    URL: Article
    DOI: 10.1002/jor.v39.10
    DOI: 10.1002/jor.24958
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2050452-4
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  • 6
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    In vitro modulation of the behavior of adhering macrophages by medications is biomaterial-dependent
    IOP Publishing ; 2017
    In:  Biomedical Materials Vol. 12, No. 2 ( 2017-03-07), p. 025006-
    Details
    In: Biomedical Materials, IOP Publishing, Vol. 12, No. 2 ( 2017-03-07), p. 025006-
    Type of Medium: Online Resource
    ISSN: 1748-605X
    URL: Article
    DOI: 10.1088/1748-605X/aa5cbc
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2017
    detail.hit.zdb_id: 2233169-4
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  • 7
    Online Resource
    Online Resource
    Intra-articular Injections of Platelet-Rich Plasma Releasate Reduce Pain and Synovial Inflammation in a Mouse Model of Osteoarthritis
    SAGE Publications ; 2018
    In:  The American Journal of Sports Medicine Vol. 46, No. 4 ( 2018-03), p. 977-986
    Details
    In: The American Journal of Sports Medicine, SAGE Publications, Vol. 46, No. 4 ( 2018-03), p. 977-986
    Abstract: Osteoarthritis (OA) is a degenerative joint disease leading to pain and disability for which no curative treatment exists. A promising biological treatment for OA is intra-articular administration of platelet-rich plasma (PRP). PRP injections in OA joints can relieve pain, although the exact working mechanism is unclear. Purpose: To examine the effects of PRP releasate (PRPr) on pain, cartilage damage, and synovial inflammation in a mouse OA model. Study Design: Controlled laboratory study. Methods: OA was induced unilaterally in the knees of male mice (n = 36) by 2 intra-articular injections of collagenase at days –7 and –5. At day 0, pain was measured by registering weight distribution on the hindlimbs, after which mice were randomly divided into 2 groups. Mice received 3 intra-articular injections of PRP or saline in the affected knee. Seven mice per group were euthanized at day 5 for assessment of early synovial inflammation and cartilage damage. Pain in the remaining mice was registered for a total of 3 weeks. These mice were euthanized at day 21 for assessment of cartilage damage and synovial inflammation on histological evaluation. Antibodies against iNOS, CD163, and CD206 were used to identify different subtypes of macrophages in the synovial membrane. Results: Mice in the PRPr group increased the distribution of weight on the affected joint in 2 consecutive weeks after the start of the treatment ( P 〈 .05), whereas mice in the saline group did not. At day 21, PRPr-injected knees had a thinner synovial membrane ( P 〈 .05) and a trend toward less cartilage damage in the lateral joint compartment ( P = .053) than saline-injected knees. OA knees treated with saline showed less anti-inflammatory (CD206+ and CD163+) cells at day 5 than healthy knees, an observation that was not made in the PRPr-treated group. A higher level of pain at day 7 was associated with a thicker synovial membrane at day 21. The presence of CD206+ cells was negatively associated with synovial membrane thickness. Conclusion: In a murine OA model, multiple PRPr injections reduced pain and synovial thickness, possibly through modulation of macrophage subtypes. Clinical Relevance: PRPr injections in early OA or shortly after joint trauma can reduce pain and synovial inflammation and may inhibit OA development in patients.
    Type of Medium: Online Resource
    ISSN: 0363-5465 , 1552-3365
    URL: Article
    DOI: 10.1177/0363546517750635
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2063945-4
    SSG: 31
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  • 8
    Online Resource
    Online Resource
    Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells: an in Vitro Study
    Springer Science and Business Media LLC ; 2017
    In:  Stem Cell Reviews and Reports Vol. 13, No. 2 ( 2017-4), p. 267-277
    Details
    In: Stem Cell Reviews and Reports, Springer Science and Business Media LLC, Vol. 13, No. 2 ( 2017-4), p. 267-277
    Type of Medium: Online Resource
    ISSN: 1550-8943 , 1558-6804
    URL: Article
    DOI: 10.1007/s12015-017-9719-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2495579-6
    detail.hit.zdb_id: 2197218-7
    SSG: 12
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  • 9
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    Online Resource
    Fibrates as therapy for osteoarthritis and rheumatoid arthritis? A systematic review
    SAGE Publications ; 2013
    In:  Therapeutic Advances in Musculoskeletal Disease Vol. 5, No. 1 ( 2013-02), p. 33-44
    Details
    In: Therapeutic Advances in Musculoskeletal Disease, SAGE Publications, Vol. 5, No. 1 ( 2013-02), p. 33-44
    Abstract: Fibrates are used as lipid-lowering drugs to prevent cardiovascular pathology. Fibrates are ligands of peroxisome proliferator-activated receptor α (PPARα). Besides altering lipid metabolism, PPARα ligands exert anti-inflammatory effects on various cell types. In this study, we hypothesized that PPARα agonists exert beneficial effects on osteoarthritis (OA) and rheumatoid arthritis (RA) by their local anti-inflammatory effects, but also by their systemic influences. A systematic literature search of Medline and EMBASE databases was performed up to August 2011. The main search items were osteoarthritis, rheumatoid arthritis, peroxisome proliferator-activated receptor alpha and fibrates. Inclusion criteria were in vivo or in vitro studies regarding humans or animals in which the effects of PPARα ligands were studied. Six in vivo human studies, four in vivo animal studies and seven in vitro studies were included. The in vivo human studies showed all beneficial clinical effects of PPARα ligands, but studies were small and only four were randomized. Ligands for PPARα significantly reduced pain, swelling of the joints and decreased systemic inflammatory markers. In vitro and in vivo animal studies indicate that PPARα agonists inhibit bone resorption, and reduce inflammatory and destructive responses in cartilage and synovium. PPARα agonists such as fibrates should be considered as potential therapeutic strategy for RA. There is no clinical evidence for their use in OA, although in vitro studies indicate that PPARα agonists demonstrate different joint-protective effects locally, and systemic effects on inflammation, serum lipid levels and vascular pathology. Animal studies should be performed and after confirmation of the protective effects of PPARα, large randomized controlled trials could investigate fibrates in OA and RA.
    Type of Medium: Online Resource
    ISSN: 1759-720X , 1759-7218
    URL: Article
    DOI: 10.1177/1759720X12468659
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2516075-8
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  • 10
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    Online Resource
    Traumatic Meniscal Tears Are Associated With Meniscal Degeneration
    SAGE Publications ; 2020
    In:  The American Journal of Sports Medicine Vol. 48, No. 10 ( 2020-08), p. 2345-2352
    Details
    In: The American Journal of Sports Medicine, SAGE Publications, Vol. 48, No. 10 ( 2020-08), p. 2345-2352
    Abstract: Meniscal tears are traditionally classified into traumatic versus degenerative tears. Although this classification plays a major role in clinical decision making, no consensus exists on the exact definition of a traumatic or degenerative tear, and the histopathological basis for this classification is unclear. Purpose: To assess the histological degree of meniscal degeneration in patients with a traumatic meniscal tear, as compared with intact meniscal tissue and osteoarthritic meniscal tissue. Study Design: Descriptive laboratory study. Methods: Traumatically torn meniscal tissue was collected during arthroscopic partial meniscectomy. As a control group, intact meniscal tissue was used from transfemoral amputations or direct postmortem dissections. Meniscal tissue from osteoarthritic knees was obtained during total knee replacement surgery. Meniscal tissue was processed, stained, and histologically analyzed with the Pauli scoring system (range, 0-18), comprising the subdomains surface integrity, cellularity, collagen organization, and matrix staining. Scoring was performed by 2 independent observers, blinded to condition, region, and patient data of the meniscus. Results: The traumatic meniscal tear group contained 43 patients (34 men; median age, 29 years; median body mass index [BMI], 24 kg/m 2 ); the intact meniscal tissue group, 8 patients (3 men; median age, 58 years; median BMI, 30 kg/m 2 ); and the osteoarthritic group, 14 patients (4 men; median age, 66 years; median BMI, 28 kg/m 2 ). After adjustment for sex, age, and BMI, patients with a traumatic meniscal tear had a significantly higher histological score than patients with intact meniscal tissue (2.7-point difference; P = .035). Histological score between the traumatic and osteoarthritic groups was not different. Conclusion: Traumatically torn menisci possess a higher degree of degeneration than intact menisci. Our results suggest that patients with a traumatic meniscal tear may already have had a certain degree of meniscal degeneration. These findings potentially challenge the classic view of traumatic versus degenerative meniscal tears. Clinical Relevance: Our findings provide a better understanding of the tissue condition of a torn meniscus. This knowledge may help clinicians decide on choice of treatment and may lead to new perspectives to prevent knee osteoarthritis in patients with a torn meniscus.
    Type of Medium: Online Resource
    ISSN: 0363-5465 , 1552-3365
    URL: Article
    DOI: 10.1177/0363546520934766
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2063945-4
    SSG: 31
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