Baicalein inhibits osteosarcoma cell proliferation and invasion through the miR­183/Ezrin pathway.

Osteosarcoma (OS), a common and primary malignant bone tumor, is characterized by highly aggressive potency. Baicalein, a bioactive flavone isolated from Scutellaria baicalensis Georgi, has been shown to inhibit the progression of numerous tumors, including OS. However, the mechanisms by which baicalein protects against OS are still largely unknown. The results of the present study showed that administration of baicalein significantly inhibited the proliferation, migration and invasion and promoted apoptosis in MG­63 and Saos­2 cells. Ezrin was identified as a target gene of microRNA (miR)­183. MG­63 and Saos­2 cells treated with baicalein exhibited increased miR­183 levels and decreased Ezrin expression. Importantly, miR­183 inhibition and Ezrin overexpression abolished the effects of baicalein on MG­63 and Saos­2 cell proliferation, migration, invasion and apoptosis. Taken together, these findings suggest that baicalein inhibits the proliferation, migration and invasion and induces apoptosis in OS cells by activating the miR­183/Ezrin pathway, revealing a novel mechanism underlying anti­OS effects of baicalein.

Autophagy: A double-edged sword in intervertebral disk degeneration.

Autophagy is a homeostatic mechanism through which intracellular damaged organelles and proteins are degraded and recycled in response to increased metabolic demands or stresses. Although primarily cytoprotective, dysfunction of autophagy is often associated with many degenerative diseases, including intervertebral disc (IVD) degeneration (IDD). As a main contributing factor to low back pain, IDD is the pathological basis for various debilitating spinal diseases. Either higher or lower levels of autophagy are observed in degenerative IVD cells. Despite the precise role of autophagy in disc degeneration that is still controversial, with difference from protection to aggravation, targeting autophagy has shown promise for mitigating disc degeneration. In the current review, we summarize the changes of autophagy in degenerative IVD cells and mainly discuss the relationship between autophagy and IDD. With continued efforts, modulation of the autophagic process could be a potential and attractive therapeutic strategy for degenerative disc disease.

Interleukin-1ß in intervertebral disk degeneration.

Intervertebral disk degeneration (IDD) is the most common diagnosis in patients with low back pain, a main cause of musculoskeletal disability in the world. Interleukin-1 (IL-1) ß is the most important member of the IL-1 family, and has a strong pro-inflammatory activity by stimulating the secretion of multiple pro-inflammatory mediators. IL-1ß is highly expressed in degenerative intervertebral disk (IVD) tissues and cells, and it has been shown to be involved in multiple pathological processes during disk degeneration, including inflammatory responses, matrix destruction, angiogenesis and innervation, cellular apoptosis, oxidative stress and cellular senescence. However, inhibition of IL-1ß is found to promote extracellular matrix (ECM) repair and protect against disk regeneration. In this review, after a brief description of IL-1ß signaling, we mainly focus on the expression profiles, roles and therapeutic potential of IL-1ß in IDD. A better understanding will help develop novel IL-1ß-based therapeutic interventions for degenerative disk disease.

MicroRNAs: New players in intervertebral disc degeneration.

Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration.