The effects of substance p on tendinopathy are dose-dependent: an in vitro and in vivo model study.

Abstract

Substance P (SP) is known to be involved in neuropathic pain, chronic inflammation, and tendinopathy. The present study evaluated the effects of different doses of SP on tendon-derived stem cells (TDSCs) in vitro and tendons in vivo. For the in vitro study, TDSCs cultured in growth medium with different concentrations of SP (negative control, 0.1 nM, and 1.0 nM). The effects of SP on TDSCs were examined with respect to their ability to proliferate and differentiate. For the in vivo study, we injected different doses of SP (saline control, 0.5 nmol, and 5.0 nmol) into rat patella tendons to investigate the effects of SP on tendons. Low and high doses SP significantly enhanced the proliferation ability of TDSCs. Low-dose of SP induced the expression of tenocyte-related genes; however, high-dose of SP induced the expression of non-tenocyte genes, which was evident by the high expression of PPARγ and collagen type II. In the in vivo study, only high-doses of SP (5.0 nmol) induced the tendinosis-like changes in the patella tendon injection model. Low doses of SP (0.5 nmol) enhanced the tenogenesis compared with saline injection and the high-dose SP group. SP enhances the proliferation of TDSCs in vitro and the effects of SP on tendinopathy are dose-dependent in vivo.