Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation

Korchi, Amine M.; Cengarle-Samak, Alexandre; Okuno, Yuji; Martel‐Pelletier, Johanne; Pelletier, Jean Pierre; Boesen, Mikael; Doyon, Josée; Bodson-Clermont, Paule; Lussier, Bertrand; Héon, Hélène; Sapoval, M.; Bureau, Nathalie J.; Soulez, Gilles

doi:10.1016/j.jvir.2018.09.031

Cited by 31 publications

(23 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…WORMS analysis revealed a significant improvement in synovitis across all patients, with no significant cartilage loss. This finding was also reported by Okuno et al [9], and is aligned with the hypothesis that synovial hypervascularity is an important factor in the pathological process of knee OA, which may be exploited by GAE to reduce pain and improve function [16,22]. WORMS analysis also found a significant deterioration in osteophytes and bone attrition, not previously reported.…”

Section: Discussionsupporting

confidence: 90%

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis

Little

Gibson

Briggs

et al. 2021

Cardiovasc Intervent Radiol

View full text Add to dashboard Cite

Purpose Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. Methods Thirty-eight patients, median age = 60 (45–83), attended for GAE using 100–300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0–100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. Results Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53–66) at baseline to 36 (SD = 24, 95% CI 28–44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30–60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis. Conclusion GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

show abstract

Section: Discussionsupporting

confidence: 90%

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis

Little

Gibson

Briggs

et al. 2021

Cardiovasc Intervent Radiol

View full text Add to dashboard Cite

show abstract

“…Korchi et al found signs of synovial inflammation and hypervascularization already 3 months after OA onset in an animal model of early OA by analyzing radiological and histological changes [ 18 ]. Interestingly, the amount of CD4 + T cells expressing CCR5 in SM and SF of our early OA patients is comparably high as previously described in SF of patients with different forms of rheumatic joint diseases such as RA, psoriatic arthritis, and ankylosing spondylitis [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis

et al. 2021

View full text Add to dashboard Cite

Background Investigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to characterize the involved cell populations, by investigating synovial fluid (SF) and synovial membrane (SM) of early OA patients for the presence and polarization status of CD4 T cells. Methods A quantitative analysis of CD4+ T cell infiltration in SF and SM compared to peripheral blood (PB) was performed in patients with early stages of OA. We further investigated intracellular staining (ICS), surface marker, and chemokine receptor expression profiles of CD4+ T cells in SF, SM, and PB, as well as cytokine expression in native SF and PB. Matched samples of SF, SM, and PB were harvested from 40 patients with early OA at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Samples were analyzed by flow cytometry for surface markers and cytokines, which are preferentially expressed by distinct T cell subsets (Th1, Th2, Th17, regulatory T cells). Furthermore, we analyzed native SF and PB supernatants using MACSPlex for multiple cytokine expression profiles. Results SF and SM showed a distinct infiltration of CD4+ T lymphocytes, with significantly increased expression of chemokine receptors CXCR3/CCR5, cytokine IFN-γ (preferentially expressed by Th1 cells), and CD161 (preferentially expressed by IL-17 producing Th17 cells) compared to PB. Furthermore, the percentage of CD4+ T cells polarized to Treg was significantly increased in SM compared to SF and PB. No significant differences were observed for CCR3 and CCR4 (preferentially expressed by Th2 cells), although IL-4 values were significantly higher in SM and SF compared to PB. Cytokine analysis showed comparable results between PB and SF, with only IL-6 being significantly increased in SF. Conclusions Early OA joints show already significant inflammation through CD4+ T cell infiltration, with predominant Th1 cell polarization. Inflammation seems to be driven by direct proinflammatory cell interaction. Cytokine signaling seems to be negligible at the site of inflammation in early OA, with only IL-6 being significantly increased in SF compared to PB.

show abstract

“…How dysregulated vascularization contributes to intraarticular ligament degeneration in OA remains unclear. It is known that angiogenesis is increased in other joint tissues affected by OA [46], particularly hypervascularization of the inflamed synovial membrane can be observed (Figure 3), which is also a source for ACL nutrition, but also blood vessels penetrating the osteochondral junction, the inner parts of the menisci, and osteophytes can be detected [47,48,49]. In addition, some degenerated ACLs show hypervascularization of the midsubstance (Figure 4).…”

Section: Anatomy Of Intraarticular Ligaments Of the Kneementioning

confidence: 99%

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Schulze‐Tanzil

2019

Cells

View full text Add to dashboard Cite

Osteoarthritis (OA) induces inflammation and degeneration of all joint components including cartilage, joint capsule, bone and bone marrow, and ligaments. Particularly intraarticular ligaments, which connect the articulating bones such as the anterior cruciate ligament (ACL) and meniscotibial ligaments, fixing the fibrocartilaginous menisci to the tibial bone, are prone to the inflamed joint milieu in OA. However, the pathogenesis of ligament degeneration on the cellular level, most likely triggered by OA associated inflammation, remains poorly understood. Hence, this review sheds light into the intimate interrelation between ligament degeneration, synovitis, joint cartilage degradation, and dysbalanced subchondral bone remodeling. Various features of ligament degeneration accompanying joint cartilage degradation have been reported including chondroid metaplasia, cyst formation, heterotopic ossification, and mucoid and fatty degenerations. The entheses of ligaments, fixing ligaments to the subchondral bone, possibly influence the localization of subchondral bone lesions. The transforming growth factor (TGF)β/bone morphogenetic (BMP) pathway could present a link between degeneration of the osteochondral unit and ligaments with misrouted stem cell differentiation as one likely reason for ligament degeneration, but less studied pathways such as complement activation could also contribute to inflammation. Facilitation of OA progression by changed biomechanics of degenerated ligaments should be addressed in more detail in the future.

show abstract

Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation

Cited by 31 publications

References 32 publications

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis

Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Contact Info

Product

Resources

About