Inflammation plays an important role in the development and resolution of tendon diseases, but underlying mechanisms are poorly understood. We therefore aimed to analyze the response of human tenocytes to inflammatory stimuli and to uncover their interplay with macrophages in vitro. Tenocytes from human ruptured supraspinatus tendons (n = 10) were treated for three days with a stimulation mixture derived from activated mononuclear cells isolated from healthy human peripheral blood. Significantly increased expression levels of selected adhesion- and human leukocyte antigen (HLA)-molecules, and enhanced interleukin (IL)-6 release were detected by flow cytometry. Tenocyte stimulation with the pro-inflammatory cytokines interferon gamma, tumor necrosis factor alpha and IL-1ß triggered similar changes in surface markers and enhanced the release of IL-6, IL-8 and monocyte chemoattractant protein 1 (MCP-1). In co-cultures of macrophages with pre-stimulated tenocytes, macrophages significantly increased CD80 expression, but simultaneously decreased HLA-DR-expression, which are both typical pro-inflammatory polarization markers. Co-cultures also released more IL-6, IL-8, MCP-1 than tenocyte-cultures alone. We demonstrate that tenocytes respond to inflammatory environments in vitro with altered surface marker and cytokine profiles and influence macrophage polarization. Importantly, all changes detected in direct co-cultures were also present in a transwell setting, implicating that communication between the cells involves soluble factors.

Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7), chronic ruptures (n = 6), acute ruptures (n = 13), and intact tendons (n = 4) were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR) analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases) in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation (interleukin (IL) 1β, tumor necrosis factor α, IL6, IL10, IL33, soluble ST2, transforming growth factor β1, cyclooxygenase 2), inflammatory cells (cluster of differentaition (CD) 3, CD68, CD80, CD206), fat metabolism (fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, adiponectin), and innervation (protein gene product 9.5, growth associated protein 43, macrophage migration inhibitory factor) were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies.