The endoplasmic reticulum is a critical organelle for normal cell function and homeostasis. Disturbed protein folding process in the ER, termed ER stress, leads to the activation of unfolded protein response (UPR) that encompasses a complex network of intracellular signaling pathways. The UPR can either restore ER homeostasis or activate pro-apoptotic pathways depending on specific insults, intensity and duration of the stress, and cell types. ER stress and the UPR have recently been linked to inflammation in a variety of human pathologies including autoimmune diseases, infection, neurodegenerative disease, and metabolic disorders. In the cell, ER stress and inflammatory signaling share extensive regulators and effectors in a broad spectrum of biological processes. In spite of different etiologies, the two signaling pathways were shown to form a vicious cycle in exacerbating cellular dysfunction and causing apoptosis in many cells and tissues. However, the interaction between ER stress and inflammation in many of these diseases remains elusive. Further understanding of those issues may enable the development of novel therapies that spontaneously target these pathogenic pathways.

Long noncoding RNAs (lncRNAs), which serve as important and powerful regulators of various biological activities, have gained widespread attention in recent years. Emerging evidence has shown that some lncRNAs play important regulatory roles in osteoblast differentiation of mesenchymal stem cells (MSCs), suggesting a potential therapeutic strategy for bone fracture. As a recently identified lncRNA, linc-ROR was reported to mediate the reprogramming ability of differentiated cells into induced pluripotent stem cells (iPSCs) and human embryonic stem cells (ESCs) self-renewal. However, other functions of linc-ROR remain elusive. In this study, linc-ROR was found to be upregulated during osteogenesis of human bone-marrow-derived MSCs. Ectopic expression of linc-ROR significantly accelerated, whereas knockdown of linc-ROR suppressed, osteoblast differentiation. Using bioinformatic prediction and luciferase reporter assays, we demonstrated that linc-ROR functioned as a microRNA (miRNA) sponge for miR-138 and miR-145, both of which were negative regulators of osteogenesis. Further investigations revealed that linc-ROR antagonized the functions of these two miRNAs and led to the de-repression of their shared target ZEB2, which eventually activated Wnt/β-catenin pathway and hence potentiated osteogenesis. Taken together, linc-ROR modulated osteoblast differentiation by acting as a competing endogenous RNA (ceRNA), which may shed light on the functional characterization of lncRNAs in coordinating osteogenesis.

Patients with diabetes are at great risk to suffer many musculoskeletal disorders, such as tendinopathy, tendon rupture and impaired tendon healing. However, the pathogenesis of these tendon disorders still remains unclear. In this study, we aimed to investigate the effects of high glucose on cell proliferation, cell apoptosis and tendon-related markers expression of tendon-derived stem cells (TDSCs) in vitro. These findings might provide new insights into the pathogenesis of diabetic tendon disorders. The cell proliferative ability and apoptosis rate of TDSCs in different groups were evaluated by MTT assay and Annexin V-FITC/PI staining assay. The mRNA expression of tendon-related markers (Scleraxis and Collagen I alpha 1 chain) were assessed by qRT-PCR. The protein expression of tendon-related markers (Tenomodulin and Collagen I) were measured by Western blotting. The proliferative ability of TDSCs treated with high glucose (15mM and 25mM) decreased significantly at day1, day3 and day5. The cell apoptosis of TDSCs increased significantly when they were cultured with high glucose for 48h in vitro. The gene expression of Scleraxis and Collagen I alpha 1 chain in TDSCs decreased significantly when they were treated with high glucose for 24h and 48h. The protein expression of Tenomodulin and Collagen I in TDSCs decreased significantly when they were treated with high glucose for 24h and 48h. High glucose could inhibit cell proliferation, induce cell apoptosis and suppress the tendon-related markers expression of TDSCs in vitro. These findings might account for some pathological mechanisms underlying the pathogenesis of diabetic tendon disorders.