Tendon stem/progenitor cells regulate inflammation in tendon healing via JNK and STAT3 signaling

Abstract

Tendon stem/progenitor cells (TSCs) have been found in different anatomic locations and showed a promising regenerative potential. We identified a role of TSCs in the regulation of inflammation during healing of acute tendon injuries. Delivery of connective tissue growth factor (CTGF) into full-transected rat patellar tendons significantly increased the number of CD146 + TSCs, leading to enhanced healing. In parallel, CTGF delivery significantly reduced the number of iNOS + M1 macrophages and increased the expression of anti-inflammatory IL-10 at 2 d after surgery, with over 85%

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

“…Persistently active STAT3 has been identified in many human cancers and appears to be required for the continued growth or resistance to apoptosis of cultured human cancer cells. 20,25,41,42 In this study, phospho-JNK activation in- Additionally, several reports have demonstrated that there are interacting regions in STAT3 and c-Jun that participate in cooperative transcriptional activation. 14,18,19,43 These concepts support our finding that phospho-STAT3 was suppressed by the activation of phospho-JNK and phospho-c-Jun.…”

“…Our research team has reported that inhibition of STAT3 phosphorylation has beneficial clinical therapeutic effects on human osteosarcoma. Persistently active STAT3 has been identified in many human cancers and appears to be required for the continued growth or resistance to apoptosis of cultured human cancer cells . In this study, phospho‐JNK activation induced significant phospho‐STAT3 degradation.…”

“…9,10,14,15 Some reports have indicated that there is an interaction between a region within c-Jun and specific sites within signal transducer and activator of transcription 3 (STAT3) in vitro and in vivo. [16][17][18][19] Additionally, JNK is an upstream kinase responsible for the phosphorylation of STAT3, 16,[20][21][22] and both are known to play critical roles in the regulation of apoptosis signal transduction in cancer.…”

Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair

“…While this review focused on TSPCs since these tissue‐specific cells may be “primed” toward tenogenic differentiation, pioneering early research in tendon tissue engineering applied bone marrow‐derived mesenchymal stem cells and tested strategies for optimizing their tenogenic potential via 3‐dimensional and mechanical cues . Recent studies also highlight the exciting capacity of neighboring endogenous cells to be activated and recruited toward tendon repair in vivo, given the correct molecular signals . The choice of cell type is an essential consideration which impacts the overall therapeutic strategy.…”

Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair

“…16 Furthermore, a biocompatible delivery system is required to positively impact the repairing tendon stumps, while avoiding negative inflammatory reactions that lead to the formation of adhesions, gap formation, and/or repair rupture. 17 The current study aimed to address limitations of previous biological interventions for intrasynovial flexor tendon repair by combining CTGF, a growth factor recently shown to promote tendon regeneration in rodents, [18][19][20] with a novel porous suture delivery method. 21 Lee et al recently demonstrated that CTGF embedded in a fibrin matrix can enrich tendonresident CD146 þ stem/progenitor cells and promote neovascularization, tenogenic differentiation, collagen deposition, and matrix remodeling in a rat patellar tendon surgical model.…”