Background: Cartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation. Purpose: To evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model. Study Design: Controlled laboratory study. Methods: A full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mice (N = 80). Mice received an intra-articular injection of TAA or saline on day 1 or 7 after induction of the defect. Mice were euthanized on days 10 and 28 for histological evaluation of cartilage defect repair, synovial inflammation, and synovial membrane thickness. Results: Mice injected with TAA had significantly less synovial inflammation at day 10 than saline-injected mice independent of the time of administration. At day 28, the levels of synovitis dropped toward healthy levels; nevertheless, the synovial membrane was thinner in TAA- than in saline-injected mice, reaching statistical significance in animals injected on day 1 (70.1 ± 31.9 µm vs 111.9 ± 30.9 µm, respectively; P =.01) but not in animals injected on day 7 (68.2 ± 21.86 µm vs 90.2 ± 21.29 µm, respectively; P =.26). A thinner synovial membrane was moderately associated with less filling of the defect after 10 and 28 days (r = 0.42, P =.02; r = 0.47, P =.01, respectively). Whereas 10 days after surgery there was no difference in the area of the defect filled and the cell density in the defect area between saline- and TAA-injected knees, filling of the defect at day 28 was lower in TAA- than in saline-injected knees for both injection time points (day 1 injection, P =.04; day 7 injection, P =.01). Moreover, there was less collagen type 2 staining in the filled defect area in TAA- than in saline-injected knees after 28 days, reaching statistical significance in day 1–injected knees (2.6% vs 18.5%, respectively; P =.01) but not in day 7–injected knees (7.4% vs 15.8%, respectively; P =.27). Conclusion: Intra-articular injection of TAA reduced synovial inflammation but negatively affected cartilage repair. This implies that inhibition of inflammation may inhibit cartilage repair or that TAA has a direct negative effect on cartilage formation. Clinical Relevance: Our findings show that TAA can inhibit cartilage defect repair. Therefore, we suggest not using TAA to reduce inflammation in a cartilage repair setting.

OBJECTIVE: Inflammation is known to negatively affect cartilage repair. However, it is unclear how inflammation influences the migration of mesenchymal stromal cells (MSCs) from the underlying bone marrow into the defect. We therefore aimed to investigate how synovial inflammation influences MSC migration, and whether modulation of inflammation with triamcinolone acetonide (TAA) may influence migration. DESIGN: Inflamed human osteoarthritic synovium, M(IFNγ+TNFα) pro-inflammatory macrophages, M(IL4) repair macrophages, M(IL10) anti-inflammatory macrophages, or synovial fibroblasts were cultured with/without TAA. Conditioned medium (CM) was harvested after 24 hours, and the effect on MSC migration was studied using a Boyden chamber assay. Inflammation was evaluated with gene expression and flow cytometry analysis. RESULTS: Synovium CM increased MSC migration. Modulation of synovial inflammation with TAA further increased migration 1.5-fold (P < 0.01). TAA significantly decreased TNFA, IL1B, and IL6 gene expression in synovium explants and increased CD163, a gene associated with anti-inflammatory macrophages. TAA treatment decreased the percentage of CD14+/CD80+ and CD14+/CD86+ pro-inflammatory macrophages and increased the percentage of CD14+/CD163+ anti-inflammatory macrophages in synovium explants. Interestingly, MSC migration was specifically enhanced by medium conditioned by M(IL4) macrophages and by M(IL10) macrophages treated with TAA, and unaffected by CM from M(IFNγ+TNFα) macrophages and synovial fibroblasts. CONCLUSION: Macrophages secrete factors that stimulate the migration of MSCs. Modulation with TAA increased specifically the ability of anti-inflammatory macrophages to stimulate migration, indicating that they play an important role in secreting factors to attract MSCs. Modulating inflammation and thereby improving migration could be used in approaches based on endogenous repair of full-thickness cartilage defects.

Background: Altered perfusion might play an important role in the pathophysiology of patellofemoral pain (PFP), a common knee complaint with unclear pathophysiology. Purpose: To investigate differences in dynamic contrast-enhanced (DCE)-MRI perfusion parameters between patients with PFP and healthy control subjects. Population/Subjects/Phantom/Specimen/Animal Model: Thirty-five adult patients with PFP and 44 healthy adult control subjects. Field Strength/Sequence: 3T DCE-MRI consisting of a sagittal, anterior-posterior, frequency-encoded, fat-suppressed 3D spoiled gradient-echo sequence with intravenous contrast administration. Assessment: Patellar bone volumes of interest (VOIs) were delineated by a blinded observer. Quantitative perfusion parameters (k_ep and k_trans) were calculated from motion-compensated DCE-MRI data by fitting Tofts' model. Weighted mean and unweighted median values of k_ep and k_trans were computed within the patellar bone VOIs. Statistical Tests: Differences in patellar bone perfusion parameters were compared between groups by linear regression analyses, adjusted for confounders. Results: Mean differences of weighted mean and unweighted median were 0.0039 (95% confidence interval [CI] –0.0013; 0.0091) and 0.0052 (95% CI –0.0078; 0.018) for k_trans, and 0.046 (95% CI –0.021; 0.11) and 0.069 (95% CI –0.017; 0.15) for k_ep, respectively. All perfusion parameters were not significantly different between groups (P-values: 0.32; 0.47 for k_trans, and 0.24; 0.15) for k_ep. However, a significant difference in variance between populations was observed for k_trans (P-value 0.007). Data Conclusion: Higher patellar bone perfusion parameters were found in patients with PFP when compared to healthy control subjects, but these differences were not statistically significant. This result, and the observed significant difference in k_trans variance, warrant further research. Level of Evidence: 1. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2018;47:1344–1350.