Background and Aims Tendon-derived stem cells (TDSCs) in tendons are responsible for tenogenesis and tendon regeneration. Aberrant nontenogenic differentiation of TDSCs, such as chondrogenic metaplasia, have been suggested as a pathogenesis of tendinopathy. Additionally, pain mediators, such as substance P, calcitonin gene-related peptide (CGRP) and macrophage migration inhibitory factor (MIF), have been increasingly discussed as an important factor in the pathogenesis of tendinopathy. The purpose was to evaluate whether the pain mediator affects differentiation of TDSC.
Methods TDSC was isolated and cultured from the Achilles tendon of SD rats. TDSC were treated with recombinant MIF, recombinant substance P, or recombinant CGRP. For gene knockdown, TDSC were transfected with MIF small interfering RNA (siRNA), substance P siRNA, or CGRP siRNA. The TDSC culture mediums were prepared for RT-PCR. Expression of tenogenic genes (SCX, Egr1, Tnmd, Col type 1) and chondrogenic genes (BMP2, aggrecan, Sox9) of TDSC were compared with control group.
Results Treatment of recombinant pain mediators (MIF, Substance P or CGRP) in TDSC showed down-regulated tenogenic genes expression (figure 1A, 2A, 3A) and up-regulated chondrogenic genes expression (Fig 1B, 2B, 3B) compared with control (p<.05). Knockdown of pain mediator genes (MIF, Substance P or CGRP) in TDSC showed down-regulated chondrogenic gene expression (figure 1B, 2B, 3B) while expression was up-regulated in a few tenogenic gene (Col type 1 with MIF and SCX with Substance P).
Conclusions Pain mediators, such as Substance P, CGRP and MIF, appear to be associated with pathogenesis of tendinopathy via enhance the aberrant chondrogenic differentiation and suppression of tenogenic differentiation of TDSC.
[18-100-D3-N] Protocol Approval of Animal Study Plan
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