Bradykinin protects nucleus pulposus cells from tert-butyl hydroperoxide-induced damage and delays intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential.

S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

Periostin: an emerging activator of multiple signaling pathways.

Matricellular proteins are responsible for regulating the microenvironment, the behaviors of surrounding cells, and the homeostasis of tissues. Periostin (POSTN), a non-structural matricellular protein, can bind to many extracellular matrix proteins through its different domains. POSTN usually presents at low levels in most adult tissues but is highly expressed in pathological sites such as in tumors and inflamed organs. POSTN can bind to diverse integrins to interact with multiple signaling pathways within cells, which is one of its core biological functions. Increasing evidence shows that POSTN can activate the TGF-ß, the PI3K/Akt, the Wnt, the RhoA/ROCK, the NF-κB, the MAPK and the JAK pathways to promote the occurrence and development of many diseases, especially cancer and inflammatory diseases. Furthermore, POSTN can interact with some pathways in an upstream and downstream relationship, forming complicated crosstalk. This article focuses on the interactions between POSTN and different signaling pathways in diverse diseases, attempting to explain the mechanisms of interaction and provide novel guidelines for the development of targeted therapies.

Intervertebral Disc Degeneration Models for Pathophysiology and Regenerative Therapy -Benefits and Limitations.

Aim: This review summarized the recent intervertebral disc degeneration (IDD) models and described their advantages and potential disadvantages, aiming to provide an overview for the current condition of IDD model establishment and new ideas for new strategies development of the treatment and prevention of IDD. Methods: The database of PubMed was searched up to May 2021 with the following search terms: nucleus pulposus, annulus fibrosus, cartilage endplate, intervertebral disc(IVD), intervertebral disc degeneration, animal model, organ culture, bioreactor, inflammatory reaction, mechanical stress, pathophysiology, epidemiology. Any IDD model-related articles were collected and summarized.Results: The best IDD model should have the features of repeatability, measurability and controllability. There are a lot of aspects to be considered in the selection of animals. Mice, rats and rabbits are low-cost and easy to access. However, their IVD size and shape are more different from human anatomy than pigs, cattle, sheep and goats. Organ culture models and animal models are two options in model establishment for IDD. The IVD organ culture model can put the studying variables into the controllable system for transitional research. Unlike the animal model, the organ culture model can only be used to evaluate the short-term effects and it is not applicable in simulating the complex process of IDD. Similarly, the animal models induced by different methods also have their advantages and disadvantages. For studying the mechanism of IDD and the corresponding treatment and prevention strategies, the selection of model should be individualized based on the purpose of each study.Conclusions: Various models have different characteristics and scope of application due to their different rationales and methods of construction. Currently, there is no experimental model that can perfectly mimic the degenerative process of human IVD. Personalized selection of appropriate model based on study purpose and experimental designing can enhance the possibility to obtain reliable and real results.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.