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- W3019833029 abstract "Purpose: Synovium-derived mesenchymal stem cells (MSCs) have a high proliferative and chondrogenic potential in vitro and the intra-articular transplantation of MSCs have been reported to be useful for repair of articular cartilage and meniscus. Although synovium-derived MSCs have been explored to become a new treatment for the regeneration cartilage, synovium-resident MSCs have not been identified in native joints because of a lack of specific markers. Synovial hyperplasia is common in joint injuries and arthritis, but very little is known about the identity of the synovial cells that proliferate following injury and arthritis. A previous study using a articular cartilage injury mouse model revealed that some synovial cells were quiescent and slow-cycling like adult stem cells in other tissues, showed proliferation after injury and were identified as MSCs. However, the location and kinetics of proliferating synovial cells in an arthritis model are unknown. In this study, we examined the location and cell kinetics of proliferating synovial cells in a rat knee arthritis model. Methods: We created an arthritis model by intra-articular injection of low-dose monoiodoacetic acid (MIA, 0.2mg/30μl) to knees of 8 weeks old male Wistar rats (day 0). We labeled proliferating(dividing) cells with two different artificial nucleoside analogs with intra-articular injection, chlorodeoxyuridine (CldU, 0.3mg/30μl) at day 1,2 and iododeoxyuridine (IdU, 0.3mg/30μl) at day 3,4 respectively (The experimental scheme was showed at left side in upper row of Figure 1). At day 5 and 14, rats were euthanized by CO2 gas. The whole knee joints were removed and embedded in paraffin after fixation in 4% paraformaldehyde for 1 week and decalcification in 20% EDTA for 3 weeks. 5 micrometer thick sections were made and stained with hematoxylin and eosin (HE) for histological assessment. Immunofluorescence was also performed for assessment of labeling cells with rat anti-BrdU antibody for CldU and mouse anti-BrdU antibody for IdU which were adopted in other studies using these nucleoside analogs. Reverse administration model of CldU and IdU was also created. Rats were injected IdU at day 1,2 and CldU at day 3,4 before MIA injection at day 0 (The scheme was showed at right side in upper row of Figure 1). At day 5, immunofluorescent assessment was performed. To support these labeling methods, the experiment about half-life of CldU and IdU was investigated. Rats received CldU or IdU with intra-articular injection to knees 1 day before administration of MIA and immunofluorescent assessment was perfomerd at day 5 (showed in lower row of Figure 1). Results: First of all, the experiment about half-life of CldU and IdU showed that immunofluorescence did not detect both nucleoside analogs in the whole knee joint at day 5 (data not shown). It suggests that CldU and IdU are not effective and incorporated to cells at 1 day after injection. At day 5, synovial hyperplasia was observed through cell proliferation (HE stained sections were showed in Figure 2). CldU-positive cells (which were considered to have proliferated and incorporated CldU from day 1 to day 3) were in all range of synovium and some of them also in infrapatellar fat pad, but most IdU-positive cells (which were considered to have proliferated from day 3 to 5) were in superficial layer (Immunofluorescence sections were showed at the upper row in Figure 3). At day14, synovial hyperplasia weakened and the number of CldU- and IdU-positive cells decreased and the distribution of them was not distinct (data not shown). Reverse administration model showed a reverse result in that IdU-positive cells were detected from superficial layer to deeper layer of synovium and most CldU-positive cells were in superficial layer (showed at the lower row of Figure 3). Conclusions: In this model, synovial cells proliferated from superficial layer and widened toward deeper layer chronologically. It suggests that the origin of cells to sustain synovial hyperplasia is the superficial layer of synovium, not sub-lining tissue and migrating cells from extra-joint." @default.
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- W3019833029 date "2020-04-01" @default.
- W3019833029 modified "2023-09-27" @default.
- W3019833029 title "Synovial superficial cells proliferate toward deeper layer of synovium in a rat monoiodoacetic acid induced arthritis model" @default.
- W3019833029 doi "https://doi.org/10.1016/j.joca.2020.02.322" @default.
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