Anti-osteoarthritis effect of a combination treatment with human adipose tissue-derived mesenchymal stem cells and thrombospondin 2 in rabbits

BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.

Effects of a soybean milk product on feto-neonatal development in rats

Since estrogenic pollutants and phytoestrogens can cause the disorder of the reproductive system, the effects of a soybean milk product（Vegemil^（？） containing 162 ppm isoflavones） on the feto-neonatal development, including male reproductive function, were investigated. Pregnant rats were fed the soybean milk（5% or 100% in drinking water）from gestational day（GD） 6 to parturition or to post-natal day（PND） 56. Specifically, the rats were divided into 4 groups： the control group（drinking water）, the GD5% group（5% soybean milk during only the GD period）, the GDPND5% group（5% soybean milk during the GD and PND periods）, and the GD-PND100% group（100% soybean milk instead of water during the GD and PND periods）. During the gestational, lactational, and developmental periods, the reproductive and developmental parameters of dams and offspring were observed. Feeding soybean milk did not affect the birth and physical development of both male and female offspring. At PND57, the weights of the testes and epididymides of F1 males significantly increased by feeding a high concentration of the soybean milk（GDPND100%）. In addition, feeding of the soybean milk during both the GD and PND periods（GD-PND5% and GDPND100%） enhanced the sperm counts and motility. The results indicate that soybean milk is safe for embryos,fetuses, and offspring, and improves the post-generational development of male reproductive function.