Rotator cuff tear (RCT) cause shoulder pain and motor dysfunction, which in severe cases can progress to joint degeneration and severely limit the patient’s daily activity [1]. Currently, surgical repair is the main treatment strategy for RCT. However, the data suggest that up to 94 % of rotator cuff tendons fail to heal back to bone after repair, which is the main cause of re-tearing [2]. Therefore, exploring innovative therapeutic strategies is crucial from a clinical standpoint. Healthy tendons are more than 90 % collagen, mostly type I collagen (coll I), which arranged in a precise linear pattern with dispersed tenocytes [3]. Tenocytes exist phenotypic changes in diseased tendons, leading to collagen disorder and degeneration. Tenocytes are significant factors in the development of rotator cuff disease, and their proliferation and migration have been reported to participate in tendon repair [4]. The exploration of the mechanism of tenocytes repair is expected to provide more possibilities for RCT therapy.

The most common source of mesenchymal stem cells (MSCs) is bone marrow (known as BMSCs), which can differentiate into fibroblasts, osteoblasts, chondrocytes, and tenocytes [5]. Thus, the application of BMSCs have gained much attention in recent years as a biologic therapy and have been used in a variety of procedures. Previous study suggested that BMSCs could improve the repair of RCT [6]. For example, patients who injected with MSCs had a much lower rate of re-tearing than those who received conventional treatment [7]. The function of BMSCs may be accomplished by paracrine mechanism. Exosomes could be released into the extracellular environment by various types of cells such as BMSCs [8], and usually carried functional factors such as proteins and mircoRNAs (miRNAs) to attach to or enter the receptor cells, thereby playing a role in the transmission of information in the form of autocrine or paracrine [9]. Notably, MSCs-derived exosomes (MSCs-Exo) could not only change the phenotype and function of a variety of cells such as fibrocytes [10], but also increase the content of type III collagen (coll III) by increasing the proportion of transforming growth factor TGF-β1, indicating that TGF-β1 might be beneficial to rotator cuff healing [17]. Although studies on the roles of MSCs-Exo in treating RCT are lacking, further exploration of its ability to improve RCT is a promising topic.

A wealth of miRNAs exists in exosomes and plays a critical role in angiogenesis, cell proliferation, anti-fibrosis and anti-apoptosis [11]. Therefore, the effect of miRNAs in the treatment of RCT has attracted increasing attention in recent years. For instance, As the target gene of vascular endothelial growth factor A (VEGFA), miR-205-5p was involved in the process of up-regulating collagen content and promoted tendon-bone healing of RCT [12]. The miR-29 family has been extensively studied for its role in inhibiting the production of fibrosis factors and extracellular matrix. Previous studies indicated that miR-29a prevented excessive synovial fibrosis, thereby delaying joint destruction [13], as well as the decreased levels of miR-29a in tenocytes was beneficial to the increase of coll III content [14]. Therefore, it is worth exploring whether miR-29a plays a role in rotator cuff repair.

A previous report confirmed that transforming growth factor β1 (TGF-β1) treatment could notably encourage the screction of exosomes from BMSCs [15]. Moreover, miR-29a was highly expressed in BMSCs-Exo and promoted angiogenesis and osteogenesis in osteoporosis [16]. From these findings, we warranted to know whether exosomal miR-29a derived from BMSCs was involved in the repair of RCT. Through a series of experiments, our results demonstrated that TGF-β1 treatment promoted the enrichment of miR-29a in BMSCs, thus facilitating the proliferatiion, migration, and fibrosis of tenocytes by targeting FABP3, providing an new theoretical foundation for the investigation of more effective RCT treatments.