Abstract
Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.
Highlights
Tendinopathy is common in athletes and people in many occupations involving repetitive work
The flow cytometric analysis showed that 95.3% of cells were positive for CD44 (Figure 1(c)) and 99.6% of cells were positive for CD90 (Figure 1(d)), which are stem cellrelated markers
The multilineage differentiation assay confirmed that Tendon-derived stem cells (TDSCs) were able to differentiate into adipocytes, chondrocytes, and osteocytes, Count (a)
Summary
Tendinopathy is common in athletes and people in many occupations involving repetitive work It is associated with focal tendon tenderness, activity-related pain, and decrease of strength and movement in the affected position. It was found that over 97 percent of injured tendon tissues had degenerative changes including tendolipomatosis, proteoglycan accumulation, and calcifying tendinopathy, which implied the presence of adipocytes, chondrocytes, or even osteocytes in tendinopathy. It was unclear where these nontendinous cells came from. Similar to other multipotent stem cells, TDSCs were positive for stem cell-related surface markers such as CD44, CD90, and CD146 and negative for CD34, CD45, and CD106 [3] They were able to self-renew and had adipogenic, chondrogenic, and osteogenic differentiation potentials.
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