Prostaglandin E2 (PGE2) Exerts Biphasic Effects on Human Tendon Stem Cells

Giovanni Camussi,Jianying Zhang,James H-C Wang

doi:10.1371/journal.pone.0087706

Giovanni Camussi, Jianying Zhang + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0087706

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Journal: PloS one	Publication Date: Feb 4, 2014
Citations: 37	License type: CC BY 4.0

Affiliation: University of Pittsburgh

Abstract

Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPARγ, collagen type II, and osteocalcin expression in hTSCs treated with PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo.

Highlights

Tendons transmit muscular forces to bone and, as a result, they are subjected to large mechanical loads in vivo
Effect of Prostaglandin E2 (PGE2) on the Proliferation of human tendon stem/ progenitor cells (hTSCs) After establishing that the cells in culture were hTSCs, we investigated cell proliferation after PGE2 treatment of hTSCs by determining their population doubling time (PDT)
We found that 4 weeks after implantation, non-tenocyte differentiation of hTSCs was more extensive in the cells treated with higher concentrations (10 and 100 ng/ml) of PGE2 (Fig. 9E–G, and Fig. 9I–K) when compared to the hTSCs that received the lowest concentration of PGE2 (0.1 ng/ml) (Fig. 9A–C), as evidenced by higher amounts of PPARc, collagen type II and osteocalcin

Summary

Introduction

Tendons transmit muscular forces to bone and, as a result, they are subjected to large mechanical loads in vivo. Strategies that stimulate the complete regeneration of tendons after injury have not been developed. To this end, a better understanding of tendon cell biology is essential to devise improved treatment options for tendon injuries such as tendinopathy [1]. One of the major causative factors that contribute to the development of tendinopathy is excessive mechanical loading (or overuse and over-loading) placed on tendons [2,3]. Such excessive mechanical loading has been shown to increase the production of prostaglandin E2 (PGE2) in cultures of human tendon fibroblasts (tenocytes) in vitro [3,4]. PGE2 production was shown to increase after exercise in the peritendinous space of Achilles tendons in vivo [5]

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