Abstract
Thymus-expressed chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), collagen type II (COL2A1) real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and COL2A1 expression and induced the expression of matrix metallopeptidases (MMP) 1, MMP3, early growth response protein 1 (EGR1), and superoxide dismutase 2 (SOD2). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches.
Highlights
Regenerative cell-based therapies for osteoarthritis (OA), like autologous chondrocyte implantation, have already reached clinical practice for the treatment of traumatic focal and early degenerative cartilage defects [1]
We found increased expression levels of early growth response protein 1 (EGR1) and superoxide dismutase 2 (SOD2); both being capable to suppress COL2A1 expression
For the first time, we report effects of CCL25 on chondrocyte viability and cartilage
Summary
Regenerative cell-based therapies for osteoarthritis (OA), like autologous chondrocyte implantation, have already reached clinical practice for the treatment of traumatic focal and early degenerative cartilage defects [1]. Ay, and on tissue-engineered cartilage, as depicted in the In a recent study, thymus-expressed chemokine (CCL25) was pointed out to be a candidate for experimental flow chainrstitu(Ftiisgsuue reeng6in)e.erFinog r[14c].aIrtsticlhaemgoetafcoticrmeffeacttioonnhu,mpaonrbcoinne emacrhroownMdSCrowcays tsheoswwn ien re three-dimensional (3D)-cultured for 14 dBofoagyedynesenscichnoadmihnbgeirgfoarhssf-aacdytsoe,rasnntdhsaiettxayprreemisnsivoionclvrpeordomfiinlitnahgesomsf iCcgCruaLtli2ot5nusatrinmedushlaottmeodinfMgoSorCf mbroenveeeamxleatdrrrtoahweciecnedllllusuc[t1ilo5an].r matrix (ECM), and stimulated for furtheCrCsLe25viseknnodwnatyosbewa liigtahnddofifthfeeCr-eCnmtotcifochnecmeokninterraetceipotonrs (oCCf RC9)ConLT2ce5llsaalnodndieffeorerntin combination with other cells that are located in the small intestine [16]. It plays an important role for T cell trafficking tumor necrosis factorinαthy(mTuNs aFnd-αsm).allTinhteestipneo[1r7c–i1n9]e. CXCL2 was already discussed in the context of cartilage
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