CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Abstract

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs.

Global research trends and hotspots on tendon-derived stem cell: a bibliometric visualization study

“…Activated TDSCs improve the inflammatory response in tendon tissue, increase the secretion of IL10, inhibit the polarization of macrophages towards M1 ( Tarafder et al, 2017 ), and promote the M2 polarization of macrophages ( Mao et al, 2022 ). Annexin A1 and CD200 serves as an important marker and drug target in tendon inflammatory diseases ( Liu et al, 2018 ; Giancola et al, 2022 ). Excessive inflammation may induce senescence in TDSCs.…”

Treatment with Conditioned Medium from Tenocytes Primary Cell Cultures Accelerates Histological and Functional Recovery of Achilles Tendon in Tenotomized Mice

“…Tenocytes cultures were maintained in CO 2 stove at 37 °C until reach total cellular confluence. As there are currently no protocols utilizing conditioned medium from tendon cells, the authors chose to use confluent cultures to produce the conditioned medium based on established protocols from previous tendon cell culture studies, that cultivated those cells until confluence (15,18,19). Besides that, previous analyses described that muscle and tendon-derived cells achieved higher cell numbers and full confluence more rapidly (20).…”

Dendritic Cells, Th17 Cells & Tendinopathy

“…The mean age of patients with rotator cuff tear was 60 years (53-71) -the mean tear size was 2.9 cm 2 . The mean age of the healthy tendon control group was 26 years (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

“…For, example, Stolk et al 2017 demonstrated that tenocytes in vitro responded to inflammatory environments with altered surface marker and cytokine profiles (IL-6, IL-8 and monocyte chemoattractant protein 1), inducing a pro-inflammatory macrophage polarization, 2 characterised by CD 80 expression and a decreased HLA-DR-expression [22]. Another study by Giancola et al 2022 demonstrated the role of tenocytes (tendon stem cell/progenitor cells) in releasing CD 200 ligand which binds to CD 200 receptors located on immune cells such as macrophages resulting in an upregulation of inflammatory processes during tendon injury/repair [23].…”