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. 2021 Dec;13(2_suppl):1054S-1063S.
doi: 10.1177/19476035211035435. Epub 2021 Oct 15.

Articular Cartilage Fragmentation Improves Chondrocyte Migration by Upregulating Membrane Type 1 Matrix Metalloprotease

Yunliang Lei  1 , Jiabin Peng  1   2 , Zhu Dai  1 , Ying Liao  1 , Quanhui Liu  1 , Jian Li  1 , Yonghui Jiang  1
Affiliations

Articular Cartilage Fragmentation Improves Chondrocyte Migration by Upregulating Membrane Type 1 Matrix Metalloprotease

Yunliang Lei et al. Cartilage. 2021 Dec.

Abstract

Objective: This study was undertaken to elucidate the mechanism of improved chondrocyte migration after juvenile articular cartilage fragmentation.

Design: In vitro organ culture with rabbit cartilage fragments and cell culture with rabbit chondrocytes were performed. In part A, minced juvenile cartilage fragments (~0.5 × 0.5 × 0.5 mm) from rabbits, planted in gelatin sponge and fibrin glue, were cultured for 2, 4, or 6 weeks in vitro and compared with the cartilage chunks (~4 × 4 × 1 mm) and membrane type 1 matrix metalloprotease (MT1-MMP) inhibitor groups. Chondrocyte outgrowth was evaluated on histology and confocal laser scanning microscopy. MT1-MMP expression was compared between the cartilage fragment group and the cartilage chunks group. In part B, articular chondrocytes were harvested from juvenile rabbits, MT1-MMP was transfected into the cells, and cell migration was evaluated using the Transwell and wound healing tests.

Results: The histology and confocal microscopy results revealed that cell accumulation occurred at the edge of cartilage fragments, and outgrowth was better in the cartilage fragment group than those in the cartilage chunks group. Similar results were observed for MT1-MMP expression. After MT1-MMP inhibition, cells did not accumulate at the edge of the cartilage fragments, and chondrocyte outgrowth did not occur. Furthermore, overexpression of MT1-MMP enhanced the migration of articular chondrocytes.

Conclusions: Juvenile articular cartilage fragmentation improved chondrocyte migration by upregulating MT1-MMP.

Keywords: MT1-MMP; cartilage fragmentation; chondrocyte outgrowth; in vitro.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Study design. Part A shows the in vitro organ culture of rabbit cartilage. Cartilage chunks were loaded onto the gelatin sponge and fibrin glue scaffolds and cultured in normal media (a). Minced cartilage fragments were loaded onto the gelatin sponge and fibrin glue scaffolds and cultured in normal media (b) or media containing the membrane type 1 matrix metalloprotease (MT1-MMP) inhibitor, NSC405020 (c). Part B shows the in vitro cell culture with rabbit articular chondrocytes. Rabbit articular chondrocytes were cultured in normal media (d), normal media + an empty vector (e), normal media + a vector-transfected with MT1-MMP (f), and a vector-transfected with MT1-MMP + media containing the MT1-MMP inhibitor, NSC405020 (g).
Figure 2.
Figure 2.
Histologic analysis of chondrocyte outgrowth. Sections of paraffin-embedded juvenile cartilage explants were sectioned and stained with hematoxylin and eosin (H&E). Scale bar = 500 μm. C, cartilage tissue; O, outgrowth of chondrocytes.
Figure 3.
Figure 3.
Cell accumulation at the fragments edges and fragment outgrowth was observed by confocal laser scanning microscopy. Frozen sections were sectioned and stained with EthD-III (ethidium homodimer III) and calcein AM (calcein acetoxymethyl ester). Scale bar = 200 μm. C, cartilage tissue; O, outgrowth of chondrocytes; green indicates live cells, red indicates dead cells, arrows indicate cell accumulation at the edge of the cartilage fragments. Scale bar = 200 μm.
Figure 4.
Figure 4.
Immunofluorescence demonstrating membrane type 1 matrix metalloprotease (MT1-MMP) expression. Scale bar = 100 µm, red indicates positive MT1-MMP expression, white indicates nuclei. Representative photomicrographs of groups A and B at 2 weeks (a, d), 4 weeks (b, e), and 6 weeks (c, f).
Figure 5.
Figure 5.
Chondrocyte migratory ability using the Transwell filter migration assay. Photomicrographs show chondrocyte migration after crystal violet staining, Scale bar = 200 µm. Normal medium (a); normal media + an empty vector (b); normal media + a vector-transfected with membrane type 1 matrix metalloprotease (MT1-MMP) (c); a vector-transfected MT1-MMP with + media containing the MT1-MMP inhibitor, NSC405020 (d).
Figure 6.
Figure 6.
Chondrocyte migration ability was assessed with the wound healing/scratch assay. Photographs of cell migration at 0, 24, and 48 hours of culture, Scale bar = 100 µm. Normal media (a, e, i), normal media + an empty vector (b, f, j); normal media + a vector-transfected with membrane type 1 matrix metalloprotease (MT1-MMP) (c, g, k); a vector-transfected with MT1-MMP + medium containing the MT1-MMP inhibitor, NSC405020 (d, h, l).
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References

    1. Christensen BB, Olesen ML, Hede KTC, Bergholt NL, Foldager CB, Lind M. Particulated cartilage for chondral and osteochondral repair: a review. Cartilage. Epub 2020 February 13. doi:10.1177/1947603520904757 - DOI - PMC - PubMed
    1. Farr J, Tabet SK, Margerrison E, Cole BJ. Clinical, radiographic, and histological outcomes after cartilage repair with particulated juvenile articular cartilage: a 2-year prospective study. Am J Sports Med. 2014;42(6):1417-25. - PubMed
    1. Wang T, Belkin NS, Burge AJ, Chang B, Pais M, Mahony G, et al.. Patellofemoral cartilage lesions treated with particulated juvenile allograft cartilage: a prospective study with minimum 2-year clinical and magnetic resonance imaging outcomes. Arthroscopy. 2018;34(5):1498-505. - PubMed
    1. Lanham NS, Carroll JJ, Cooper MT, Perumal V, Park JS. A comparison of outcomes of particulated juvenile articular cartilage and bone marrow aspirate concentrate for articular cartilage lesions of the talus. Foot Ankle Spec. 2017;10(4):315-321. - PubMed
    1. Seidl AJ, Kraeutler MJ. Management of articular cartilage defects in the glenohumeral joint. J Am Acad Orthop Surg. 2018;26(11):e230-7. - PubMed

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