IL-1β has been reported highly expressed in degenerative intervertebral disc, and our previous study indicated IL-1β facilitates apoptosis of human degenerative nucleus pulposus (NP) cell. However, the underlying molecular mechanism remains unclear. We here demonstrate that IL-1β played a significantly pro-apoptotic effect under serum deprivation. IL-1β decreased Bcl-2/Bax ratio and enhanced cytochrome C released from mitochondria to cytosol, which proved mitochondria-meidated apoptosis was induced. Subsequently, mitochondria damage was detected under IL-1β stimualtion. In addition, IL-1β-mediated injuried mitochondria contributes to activate autophagy. However, pretreatment with the autophagy inhibitor 3-methyladenine showed the potential in further elevating the apoptosis rate induced by IL-1β in NP cells. Our results indicated that the mitochondrial pathway was involved in IL-1β-induced apoptosis of NP cells. Meanwhile, the damaged mitochondria-induced autophagy played a protective role against apoptosis, suggesting a postive feedback mechanism under inflammatory stress.

The management of thoracolumbar (TL) burst fractures is still controversial. The thoracolumbar injury classification and severity score (TLICS) algorithm is now widely used to guide clinical decision making, however, in clinical practice, we come to realize that TLICS also has its limitations for treating patients with total scores less than 4, for which conservative treatment may not be optimal in all cases. The aim of this study is to identify several risk factors for the failure of conservative treatment of TL burst fractures according to TLICS algorithm. From June 2008 to December 2013, a cohort of 129 patients with T10-l2 TL burst fractures with a TLISC score ≤3 treated non-operatively were identified and included into this retrospective study. Age, sex, pain intensity, interpedicular distance (IPD), canal compromise, loss of vertebral body height and kyphotic angle (KA) were selected as potential risk factors and compared between the non-operative success group and the non-operative failure group. One hundred and four patients successfully completed non-operative treatment, the other 25 patients were converted to surgical treatment because of persistent local back pain or progressive neurological deficits during follow-up. Our results showed that age, visual analogue scale (VAS) score and IPD, KA were significantly different between the two groups. Furthermore, regression analysis indicated that VAS score and IPD could be considered as significant predictors for the failure of conservative treatment. The recommendation of non-operative treatment for TLICS score ≤3 has limitations in some patients, and VAS score and IPD could be considered as risk factors for the failure of conservative treatment. Thus, conservative treatment should be decided with caution in patients with greater VAS scores or IPD. If non-operative management is decided, a close follow-up is necessary.

Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering. [BMB Reports 2016; 49(3): 179-184]

Ferroptosis is an iron-dependent regulation of cell death driven by lipid peroxidation, which is intracellularly dependent on iron and independent of other metals, and morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. Ferroptosis is closely related to physiological and pathological processes, such as development, aging, and immunity, and it plays an important role in a variety of diseases. In many departments, traditional Chinese medicine plays an increasingly important role in their clinical treatment. In recent years, an increasing number of studies have been conducted on the mechanism of ferroptosis in traditional Chinese medicine. However, the role of ferroptosis in the clinical treatment of traditional Chinese medicine requires further exploration. This article mainly introduces the application of ferroptosis in studies of the mechanism of traditional Chinese medicine to help clinicians understand the current status of traditional Chinese medicine therapy for the treatment of ferroptosis-related diseases.