METHODS: A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples.
RESULTS: PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five (P <0.001) and 3.3 (P <0.001) times higher than that of the healthy group, respectively. There was no significant difference (P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples.
CONCLUSIONS AND RELEVANCE: Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.
METHODS: Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.
RESULTS: Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.
CONCLUSION: At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.
LEVEL OF EVIDENCE: II.