Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

Clinical and radiological results after one hundred fifteen MPFL reconstructions with or without tibial tubercle transfer in patients with recurrent patellar dislocation-a mean follow-up of 5.4 years.

PURPOSE: Medial patellofemoral ligament reconstruction (MPFLR) shows low recurrent rates and high satisfaction. Reports on outcome at mid-term follow-up in a large cohort with or without tibial tubercle transfer (TTT) are scarce. METHODS: One hundred six patients (115 knees; 24.3 ± 8.7 years) with recurrent patellar dislocation underwent MPFLR with ipsilateral gracilis autograft and were included in this retrospective follow-up study. In 43 knees, simultaneous TTT was performed for patellar maltracking due to patella alta or increased tibial tubercle trochlear groove distance (TT-TG). Kujala and subjective knee scores were recorded pre- and post-operatively. RESULTS: Eighty-seven percent of the patients were satisfied at a mean follow-up of 5.4 ± 3.1 years. The Kujala score increased in 81.7% of all knees from 50.9 to 76.2 points (p < 0.01). Patients with a decreased Kujala score were not different in terms of follow-up time, age, trochlear dysplasia, or post-operative patellar height. The decline was related to an increase in pain, whereas functional scores remained identical. There were six patients with persisting instability, three with patellar re-dislocation. Re-operation was necessary in 24 patients (21.2%), mainly for implant removal after TTT and loss of flexion. Performing TTT had no significant influence on the subjective outcome. Patients with more than eight years of follow-up (n = 27) did not show any difference in the subjective outcome parameters, or in osteoarthritis progression. CONCLUSION: MPFLR with and without TTT is a reliable treatment option for recurrent patellar dislocation without deterioration at mid-term follow-up. Persisting pain is a major post-operative issue that seems to be unrelated to patellofemoral anatomy.

Patellar tendinopathy with intratendinous alteration on MRI may be related to patellofemoral dysplasia.

Patellar tendinopathy (PT) is a frequent overuse injury of the extensor knee apparatus, whereas as up to 30% of the athletes might suffer from persisting symptoms during their entire career. In the present case-control study, 47 patients (30.8 ± 11.4 years) with PT with intratendinous alteration (PTita) of a minimum of ≥25% of the axial surface on MRI and minimum Blazina score of II (pain during without limiting sports activity) were included; MR images were analyzed for trochlear geometry, patellar height/tilt, and tibial tubercle-trochlear groove distance (TT-TG). The control group (CG) comprised 87 age- and gender-matched patients without history of anterior knee pain or lateral patellar instability. It was hypothesized that patients with PT might be related to patellofemoral dysplasia. It was found that the patella was significantly higher in patients with PT compared to the CG (patellotrochlear index [PT-I]: 0.33 vs 0.37, P = .014; Insall-Salvati index [InSa]: 1.18 vs 1.07, P = .004). PT-I was above the cut-off value in 10.6% of PT knees (CG 5.7%, P = .27), and InSa in 42.6% (CG 21.8%, P = .012). TT-TG was significantly higher in patients with PT compared to CG (12.0 mm vs 9.9 mm, P = .002); however, TT-TG was only pathologic (>20 mm) in one patient. The trochlear facet ratio was above the cut-off value in 55.3% of PT patients and 23% of CG (P < .001), and was significantly greater in patients with PT (0.39 ± 0.09) than CG (0.48 ± 0.1, P < .001). Knees with PT have significantly more morphological characteristics of patellofemoral instability, which needs to be considered especially in recurrent or treatment-refractive cases.