Varying regional topology within knee articular chondrocytes under simulated in vivo conditions.
ABSTRACT Topographical cartilage variation across the knee joint has been previously reported, but there is only limited information on such gene expression profiles. Articular chondrocytes from eight different topographical regions of bovine knee joints were seeded within three-dimensional scaffolds and further cultured under static conditions (unloaded control group) or subjected to an artificial joint environment within a bioreactor (loaded group). Constructs were analyzed for glycosaminoglycan (GAG), DNA, and expression of Collagen-1,-2,-10, Aggrecan, COMP, Sox9, PRG-4, PTHrp, and MMP-1,-3,-13 mRNA after 2 weeks of in vitro culture. Exclusively among loaded constructs the overall GAG production was significantly different between regions. Patella chondrocytes had overall highest, and cells from the femoral notch had overall lowest GAG/DNA under loaded conditions. Gene expression was significantly different between regions for all targets except for Sox9, PRG-4, and PTHrp among controls and with the exception of Aggrecan, Sox9, and PTHrp among loaded samples. Under mechanical stimulation Collagen-1,-2 and Aggrecan was highest at the patello-femoral joint, whereas it was lowest at typical cartilage biopsy regions. There is a clear topographical variation among distinct regions across the knee joint for gene and matrix expression profiles under static and foremost under dynamic conditions.
- SourceAvailable from: Magali Cucchiarini[Show abstract] [Hide abstract]
ABSTRACT: Associations between topographic location and articular cartilage repair in preclinical animal models are unknown. Based on clinical investigations, we hypothesized that lesions in the ovine femoral condyle repair better than in the trochlea. Full-thickness chondral and osteochondral defects were simultaneously established in the weightbearing area of the medial femoral condyle and the lateral trochlear facet in sheep, with chondral defects subjected to subchondral drilling. After 6 months in vivo, cartilage repair and osteoarthritis development was evaluated by macroscopic, histological, immunohistochemical, and biochemical analyses. Macroscopic and histological articular cartilage repair and type-II collagen immunoreactivity were better in the femoral trochlea, regardless of the defect type. Location-independently, osteochondral defects induced more osteoarthritic degeneration of the adjacent cartilage than drilled chondral lesions. DNA and proteoglycan contents of chondral defects were higher in the condyle, reflecting physiological topographical differences. The results indicate that topographic location dictates the structural patterns and biochemical composition of the repair tissue in sheep. These findings suggest that repair of cartilage defects at different anatomical sites of the ovine stifle joint needs to be assessed independently and that the sheep trochlea exhibits cartilage repair patterns reflective of the human medial femoral condyle. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res.Journal of Orthopaedic Research 06/2013; · 2.88 Impact Factor
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ABSTRACT: STUDY DESIGN: Case series: Level of evidence, 4. BACKGROUND: Arthroscopic microfracture of chondral defects across the knee joint is a frequent treatment modality. There is only limited information on the clinical outcome in patients without previous surgery and single lesions. PURPOSE: Evaluation of clinical outcome following microfracture in patients without previous surgery and single lesions and identification of prognostic factors. METHODS: Inclusion criteria were patients with single-lesion knee joint first-line microfracturing at minimum 2 years postoperatively. Charts were reviewed to identify patient and defect characteristics. Clinical outcome was evaluated by IKDC and Lysholm knee scores, Tegner activity scale and a numeric analogue scale (NAS) for function and pain (10 = highest possible function, no pain). RESULTS: Totally, 145 patients (age at operation 47.92 ± 15.7) met inclusion criteria. Average defect size was 2.7 ± 1.9 cm(2). Postoperatively, IKDC was 73.1 ± 18.5, Lysholm 77.6 ± 19.1, Tegner 4.5 ± 1.7, NAS pain 6.5 ± 2.6 and NAS function 6.4 ± 2.3. Significantly better clinical outcome was observed in male patients than in female patients. Regression analysis including all patient and defect characteristics highlighted that singly the parameter shorter symptom duration (P = 0.018) significantly predicted an improved postoperative clinical outcome. CONCLUSION: Microfracturing results in a satisfying clinical outcome, but no full recovery in patients without previous surgery and single lesions. Specific parameters facilitate outcome prognosis and therefore may aid in indicating surgery.Archives of Orthopaedic and Trauma Surgery 12/2012; · 1.36 Impact Factor
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ABSTRACT: Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca 2+ /WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca 2+ /WNT pathway was activated in OA cartilage.Cartilage 01/2012; 3:43-57.