Low back pain (LBP) is a common musculoskeletal symptom, which can be developed in multiple clinical diseases. It is widely recognized that intervertebral disc (IVD) degeneration (IVDD) is one of the leading causes of LBP. However, the pathogenesis of IVD-related LBP is still controversial, and the treatment means are also insufficient to date. In recent decades, the role of structure and function changes of sensory nervous system in the induction and the maintenance of LBP is drawing more and more attention. With the progress of IVDD, IVD cell exhaustion and extracellular matrix degradation result in IVD structural damage, while neovascularization, innervation and inflammatory activation further deteriorate the microenvironment of IVD. New nerve ingrowth into degenerated IVD amplifies the impacts of IVD-derived nociceptive molecules on sensory endings. Moreover, IVDD is usually accompanied with disc herniation, which could injure and inflame affected nerves. Under mechanical and pro-inflammatory stimulation, the pain-transmitting pathway exhibits a sensitized function state and ultimately leads to LBP. Hence, relevant pathogenic factors, such as neurotrophins, ion channels, inflammatory factors, etc., are supposed to serve as promising therapeutic targets for LBP. The purpose of this review is to comprehensively summarize the current evidence on 1) the pathological changes of sensory nervous system during IVDD and their association with LBP, and 2) potential therapeutic strategies for LBP targeting relevant pathogenic factors.

Trauma- or osteoarthritis-related cartilage damage resulted in functional decline of joints and heavy burden of public health. Recently, the reparative role of mesenchymal stem/progenitor cells (MSCs) in articular cartilage (AC) reconstruction is drawing more and more attention. To provide a review on (1) the locations and categories of joint-resident MSCs, (2) the regulation of chondrogenic capacities of MSCs, (3) the migratory approaches of MSCs to diseased AC and regulatory mechanisms. PubMed and Web of Science were searched for English-language articles related to MSC recruitment and migration for AC repair until June 2019. The presence of various MSCs in or around joints, the potential approaches to diseased AC` and the regenerative capacities of MSCs were reviewed. Various intra- and peri-articular MSCs, with inherent migratory potentials, are present in multiple stem cell niches in or around joints. The recruitment and migration of joint-resident MSCs play crucial roles in endogenous AC repair. Multiple recruiting signals, such as chemokines, growth factors, etc., emerge during the development of AC diseases and participate in the regulation of MSC mobilization. Motivated MSCs could migrate into cartilage lesions and then exert multiple reparative potentials, including extracellular matrix (ECM) reconstruction and microenvironment modulation. In general, AC repair based on endogenous MSC recruitment and migration is a feasible strategy, and a promising research field. Furthermore, endogenous AC repair mediated by native MSCs would provide new opportunities to efficient preventative or therapeutic options for AC diseases.

An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and mechanism of AFAP1-AS1 in OS (osteosarcoma) remains unclear. Quantitative reverse transcription PCR (qRT-PCR) is applied to examine AFAP1-AS1 expression in OS tissues and OS cell lines. The function of AFAP1-AS1 in OS cells is investigated via in-vitro and in-vivo assays. Western bolt and rescue experiments are applied to detect the expression changes of key molecules including epithelial-mesenchymal transition markers and identify the underlying molecular mechanism. RNA immunoprecipitation is performed to reveal the interaction between AFAP1-AS1 and RhoC. AFAP1-AS1 expression is upregulated in human OS tissues and cell lines. AFAP1-AS1 knockdown induces OS cell apoptosis and cell cycle G0/G1 arrest, suppresses OS cells growth, migration, invasion, vasculogenic mimicry formation and epithelial-mesenchymal transition (EMT), and affects actin filament integrity. AFAP1-AS1 knockdown suppresses OS tumor formation and growth in nude mice. AFAP1-AS1 knockdown elicits a signaling inhibition including decreased levels of RhoC, ROCK1, p38MAPK and Twist1. Moreover, AFAP1-AS1 interacts with RhoC. Overexpression of RhoC can partly reverse AFAP1-AS1 downregulation-induced cell EMT inhibition. AFAP1-AS1 is overexpressed in osteosarcoma and plays an oncogenic role in osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway, in which RhoC acts as the interaction target of AFAP1-AS1. Our findings indicated a novel molecular mechanism underlying the tumorigenesis and progression of osteosarcoma. AFAP1-AS1 could serve as a promising therapeutic target in OS treatment.

CXCL5 is a member of the CXC-type chemokine family, which has been found to play important roles in tumorigenesis and cancer progression. Recent studies have demonstrated that CXCL5 could serve as a potential prognostic biomarker for cancer patients. However, the prognostic value of CXCL5 is still controversial. We systematically searched PubMed, Embase and Web of Science to obtain all relevant articles investigating the prognostic significance of CXCL5 expression in cancer patients. Hazards ratios (HR) with corresponding 95% confidence intervals (CI) were pooled to estimate the association between CXCL5 expression levels with survival of cancer patients. A total of 15 eligible studies including 19 cohorts and 5070 patients were enrolled in the current meta-analysis. Our results demonstrated that elevated expression level of CXCL5 was significantly associated with poor overall survival (OS) (pooled HR 1.70; 95% CI 1.36–2.12), progression-free survival (pooled HR 1.65; 95% CI 1.09–2.49) and recurrence-free survival (pooled HR 1.49; 95% CI 1.15–1.93) in cancer patients. However, high or low expression of CXCL5 made no difference in predicting the disease-free survival (pooled HR 0.63; 95% CI 0.11–3.49) of cancer patients. Furthermore, we found that high CXCL5 expression was associated with reduced OS in intrahepatic cholangiocarcinoma (HR 1.91; 95% CI 1.31–2.78) and hepatocellular carcinoma (HR 1.87; 95% CI 1.55–2.27). However, there was no significant association between expression level of CXCL5 with the OS in lung cancer (HR 1.25; 95% CI 0.79–1.99) and colorectal cancer (HR 1.16; 95% CI 0.32–4.22, p = 0.826) in current meta-analysis. In conclusion, our meta-analysis suggested that elevated CXCL5 expression might be an adverse prognostic marker for cancer patients, which could help the clinical decision making process.