Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1115
Peer-review started: February 27, 2019
First decision: August 1, 2019
Revised: October 14, 2019
Accepted: November 4, 2019
Article in press: November 4, 2019
Published online: December 26, 2019
Mesenchymal stem cells (MSCs) reportedly differentiate into chondrocytes and have a potential for articular cartilage regeneration. Therefore, they may be a novel strategy for osteoarthritis (OA) treatment.
Since MSCs can be differentiated into osteocytes, adipocytes, and other cells, in addition to chondrocytes, the efficiency for OA treatment is limited. We tried to increase the ratio of chondrocytic differentiation of human adipose-derived MSCs (hADMSCs) with thrombospondin 2 (TSP2), thereby enhancing OA therapeutic efficacy.
The present study investigated whether TSP2 induces the chondrogenic differentiation of hADMSCs and potentiates the therapeutic effects of hADMSCs in OA rabbits.
In vitro, the chondrogenic potential of TSP2 in hADMSCs was investigated by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 siRNA-treated stem cells. In vivo, hADMSCs were injected into the injured knees of OA rabbits alone or in combination with TSP2, and OA progression was monitored via gross, radiological, and histological examinations.
In hADMSC culture, TSP2 increased the expression of chondrogenic markers as well as NOTCH signaling genes, which were inhibited by TSP2 siRNA treatment. In vivo, combination treatment with hADMSCs and TSP2 not only attenuated cartilage degeneration, osteophyte formation, and extracellular matrix loss, but also decreased synovial inflammatory cytokines.
TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling, and combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.
We demonstrated the positive roles of TSP2 in the chondrogenic differentiation of hADMSCs and in OA therapy. TSP2 could be an adjunct therapeutic for enhancing the cartilage-restoring efficacy of hADMSCs.