Journal
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 13, Issue 9, Pages 1618-1628Publisher
WILEY
DOI: 10.1002/term.2916
Keywords
articular cartilage; autophagy; conditioned medium; MSCs; osteoarthritis; subchondral bone
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Funding
- Shanghai Rising-Star Project [18QB1400500]
- The introduction project of clinical medicine expert team for Suzhou [SZYJTD201714]
- Key Clinical Medicine Center of Shanghai [2017ZZ01006]
- Development Project of Shanghai Peak Disciplines-Integrative Medicine [20180101]
- National Key R&D Program of China [2016YFC1100300, 2017YFC0840100, 2017YFC0840106]
- National Natural Science Foundation of China [81572108, 81772339]
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Evidence accumulated that mesenchymal stem cell (MSC) therapy ameliorated osteoarthritis (OA) via paracrine effect, whereas conditioned medium (CM) of MSCs contains all the secretomes. In vitro studies have proved its therapeutic effect in OA, but few in vivo evidences were unveiled. This study investigated the effect of MSCs-CM in an animal model of OA. OA was induced by anterior cruciate ligament transaction and destabilization of the medial meniscus in 12 rats bilaterally. The CM group (N = 6) was administered with intraarticular injection of MSCs-CM weekly, whereas the phosphate-buffered saline (PBS) group (N = 6) was injected with PBS. Six rats served as normal control and received sham operation with weekly PBS injection. Rats were sacrificed 8 weeks postoperatively. Gross and histological morphology were analysed. Microcomputed tomography was applied to assess the subchondral bone. Components of extracellular matrix (ECM) including type II collagen (Col II) and aggrecan, and ECM homeostasis-related enzymes (metalloproteinase-13 [MMP-13] and tissue inhibitor of metalloproteinase-1 [TIMP-1]), as well as autophagy markers (Beclin-1 and microtubule-associated protein light chain 3) were evaluated immunohistochemically. Chondrocyte apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining. Gene expression of Col II, aggrecan, MMP-13, and TIMP-1 was confirmed by real-time polymerase chain reaction. Morphological outcomes demonstrated remarkable articular-protective effect of MSCs-CM. Well-maintained subchondral bone structure, significantly more abundant cartilage matrix, notably decreased ratio of MMP-13 to TIMP-1, and inhibited chondrocyte apoptosis with enhanced autophagy were observed in the CM group compared with the PBS group. In conclusion, MSCs-CM demonstrated satisfactory effect in alleviating OA in rats via protecting the microarchitecture of subchondral bone, balancing the ratio of MMP-13 to TIMP-1 in cartilage, and enhancing autophagy, which might provide a new remedy against OA.
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