FGF23 protects osteoblasts from dexamethasone-induced oxidative injury.

Dexamethasone (DEX) can exert a cytotoxic effect on cultured osteoblasts. The current study explored the potential osteoblast cytoprotective effect of fibroblast growth factor 23 (FGF23). In OB-6 human osteoblastic cells and primary murine osteoblasts, FGF23 induced phosphorylation of the receptor FGFR1 and activated the downstream Akt-S6K1 signaling. FGF23-induced FGFR1-Akt-S6K phosphorylation was largely inhibited by FGFR1 shRNA, but augmented with ectopic FGFR1 expression in OB-6 cells. FGF23 attenuated DEX-induced death and apoptosis in OB-6 cells and murine osteoblasts. Its cytoprotective effects were abolished by FGFR1 shRNA, Akt inhibition or Akt1 knockout. Conversely, forced activation of Akt inhibited DEX-induced cytotoxicity in OB-6 cells. Furthermore, FGF23 activated Akt downstream nuclear-factor-E2-related factor 2 (Nrf2) signaling to alleviate DEX-induced oxidative injury. On the contrary, Nrf2 shRNA or knockout almost reversed FGF23-induced osteoblast cytoprotection against DEX. Collectively, FGF23 activates FGFR1-Akt and Nrf2 signaling cascades to protect osteoblasts from DEX-induced oxidative injury and cell death.

miR-1285-3p is a potential prognostic marker in human osteosarcoma and functions as a tumor suppressor by targeting YAP1.

BACKGROUND: Despite the major advances in the treatment, the overall survival of osteosarcoma remains poor. MicroRNAs (miRNAs) are involved in tumorigenesis and progression though modulating their target genes. In the present study, the roles of miR-1285-3p in osteosarcoma was investigated. METHODS: Microarray profiling was applied to distinguish the up and down regulated microRNAs in osteosarcoma. Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-1285-3p and YAP1 expression. MTT and transwell assays were carried out to determine the cells proliferation and invasion respectively. Moreover, dual luciferase reporter assay was performed to evaluate the binding efficiency between miR-1285-3p and the 3'UTR of YAP1. RESULTS: MiR-1285-3p was down regulated in osteosarcoma tissues and cell lines and the reduction of miR-1285-3p expression predicted a poor overall survival of osteosarcoma patients. Ectopic expression of miR-1285-3p inhibited osteosarcoma cell proliferation, colony formation and invasion. In addition, YAP1 was further demonstrated as a direct target of miR-1285-3p. Moreover, overexpression of YAP1 reversed the inhibitory effects of miR-1285-3p on osteosarcoma cells proliferation and invasion. CONCLUSIONS: MiR-1285-3p which was low expressed in osteosarcoma inhibited the proliferation and invasion of osteosarcoma cells via direct targeting YAP1. These results suggested that miR-1285-3p might be a potential therapeutic targets and biomarker in osteosarcoma.

SP1-mediated upregulation of lncRNA ILF3-AS1 functions a ceRNA for miR-212 to contribute to osteosarcoma progression via modulation of SOX5.

Long noncoding RNA ILF3-AS1 (ILF3-AS1) has been reported to be abnormally expressed in several tumors. However, its expression pattern and function in osteosarcoma have not been investigated. In this study, we showed that ILF3-AS1 expression was significantly up-regulated in both osteosarcoma tissues and cell lines. We first reported that ILF3-AS1 upregulation was induced by nuclear transcription factor SP1. Clinical assays revealed that higher expression of ILF3-AS1 was associated with advanced clinical stage, distant metastasis and shorter overall survival. in multivariate analysis, ILF3-AS1 expression level was found to be an independent prognostic factor for osteosarcoma patients. Functional investigations showed that knockdown of ILF3-AS1 suppressed the proliferation, migration and invasion of osteosarcoma cells, and promoted apoptosis. Bioinformatic software predicted that miR-212 both targeted the 3'-UTR of ILF3-AS1 and SOX5, which was confirmed using luciferase reporter assay, RT-PCR and Western blot. Taken together, ILF3-AS1 displayed its tumor-promotive roles in the progression of osteosarcoma through miR-212/SOX5 axis. Our findings help to elucidate the tumorigenesis of osteosarcoma, and future study will provide a novel therapeutic target for osteosarcoma.

TWEAK/Fn14 signaling: a promising target in intervertebral disc degeneration.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent chemoattractant cytokine with various biological functions, such as stimulation of angiogenesis, induction of proinflammatory cytokines, regulation of cellular proliferation and apoptosis. Therefore, it has also been implicated in several pathological processes, from cancer to inflammatory diseases. Remarkably, TWEAK and its receptors, fibroblast growth factor inducible 14 (Fn14), are also present in intervertebral disc (IVD) tissue, where they play a role in the pathogenesis of IVD degeneration. The interaction of TWEAK with Fn14 is involved in physiological and pathological activities of IVD degeneration patients, which includes apoptosis of endplate chondrocytes, extracellular matrix degradation, reduction in proteoglycan synthesis and so on. The blockade of this interaction results in suppressing over-production of proinflammatory factors and cell death in in vivo or in vitro experiments, suggesting that TWEAK/Fn14 signaling may be therapeutically relevant in IVD degeneration, and the targeting of TWEAK or Fn14 has been proposed as a potential therapeutic approach for autoimmune diseases such as Rheumatoid arthritis (RA). In this article, we discuss the biological features of TWEAK/Fn14 signaling and summarize recent advances in our understanding of the role of TWEAK/Fn14 signaling in the pathogenesis and treatment of IVD degeneration. We think that the blockade of TWEAK/Fn14 signaling may be a promising therapeutic strategy for IVD degeneration in the near future.

Tibial Tuberosity Avulsion Fracture and Open Proximal Tibial Fracture in an Adult: A Case Report and Literature Review.

A displaced tibial tuberosity avulsion fracture associated with an open extra-articular proximal tibial diaphyseal fracture is an uncommon fracture pattern. This case report describes the successful management of such a fracture pattern in a 45-year old male using an open reduction and lag screw fixation of the tuberosity with a minimally invasive reduction and plate fixation of the proximal tibial diaphyseal fracture. A literature search was done to determine the expected clinical outcome of this fracture pattern. This is the first reported adult case of an avulsion fractures of the tibial tuberosity associated with an open proximal tibial diaphyseal fracture successfully treated by an anatomical reduction and fixation of the avulsion fracture of the tibial tuberosity combined with minimally invasive percutaneous plate osteosynthesis of the proximal tibial diaphyseal fractures.

Restoration of femoral offset, rotation centers, limbs length equality of Chinese total hip arthroplasty patients.

OBJECTIVE: To explore the restoration of femoral offset, rotation centers, limbs length equality of Chinese total hip arthroplasty patients with careful preoperative surgical planning, the appropriate prosthesis and skillful manipulation combined with a variety of verification tests during the operation. METHODS: There were 92 hips (from 92 patients) surgery was performed by the same surgeon using the posterlateral approach by careful preoperative surgical planning. Appropriate prosthesis was chosen determining the reasonable femur osteotomy location, skillful manipulation and paying attention to every detail combined with a variety of verification tests and preoperative measurements during the operation. We evaluated the offset and rotation centers of the healthy (not performed) side and the operated side, the preoperative and postoperative limbs length discrepancy and analyzed the change of femoral offset, rotation centers and limbs length discrepancy of THA patients by self-control. RESULTS: We found that the preoperative and postoperative femoral offset was basically not changed, the postoperative rotation centers had a tendency to the medial and inferior of the original rotation centers, the limbs length discrepancy and Harris Hip Score (HHS) were improved much more than before. CONCLUSIONS: Careful preoperative surgical planning, the appropriate prosthesis and skillful manipulation combined with a variety of verification tests during the operation is significantly correlated to the remarkable radiological and clinical results of THA patients.