Abstract
BackgroundLow-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, although the mechanism of its potential effects on chondrogenic differentiation is unknown. Since autophagy is known to regulate the differentiation of MSCs, the aim of our study was to determine whether LIPUS induced chondrogenesis via autophagy regulation.MethodsMSCs were isolated from the rat bone marrow, cultured in either standard or chondrogenic medium, and stimulated with 3 MHz of LIPUS given in 20% on–off cycles, with or without prior addition of an autophagy inhibitor or agonist. Chondrogenesis was evaluated on the basis of aggrecan (AGG) organization and the amount of type II collagen (COL2) and the mRNA expression of AGG, COL2, and SRY-related high mobility group-box gene 9 (SOX9) genes.ResultsLIPUS promoted the chondrogenic differentiation of MSCs, as shown by the changes in the extracellular matrix (ECM) proteins and upregulation of chondrogenic genes, and these effects were respectively augmented and inhibited by the autophagy inhibitor and agonist.ConclusionsTaken together, these results indicate that LIPUS promotes MSC chondrogenesis by inhibiting autophagy.
Highlights
Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, the mechanism of its potential effects on chondrogenic differentiation is unknown
Effects of autophagy agonist and inhibitor on MSCs The protein expression of autophagy-related gene Beclin1 and LC3 in MSCs was examined by western-blot analysis after rapamycin or 3-MA treatment for 24 h
The morphometric ultrastructural analyses showed that autophagosomes were increased in rapamycin treatment group compared with the control group and 3-MA treatment group in MSCs (Fig. 1c)
Summary
Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, the mechanism of its potential effects on chondrogenic differentiation is unknown. Articular cartilage injury is a common complication of joint diseases like osteoarthritis. Due to its low innervation, poor blood supply, and low chondrocyte proliferation and migration, autologous cartilage repair capacity is very limited and can lead to irreversible joint dysfunction after injury [1]. The current therapeutic strategies of alleviating articular cartilage injury have unsatisfactory clinical outcomes. Cartilage engineering can be a promising option [2], the poor regenerative capacity of chondrocytes precludes their use as the seeding cells [3]. Mesenchymal stem cells (MSCs) are highly proliferative self-renewing cells with multi-lineage differentiation ability and have become the most promising cell source for cartilage regeneration.
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