Crosstalk between Autophagy and Apoptosis in Intervertebral Disc Degeneration

Objective: To describe the relationship between autophagy and apoptosis and the possible signaling pathways involved in degenerative lumbar intervertebral disc. Summary of Background Data: Autophagy and apoptosis are regulatory cellular mechanisms that determine many pathologies, including degenerative intervertebral disc disease. The interactions between these events in the damage or protection of intervertebral disc cells and in cellular homeostasis remain controversial. Methods: The sample size was twenty patients who underwent lumbar spine surgery for symptomatic disc herniation or spondylolisthesis. Intervertebral discs were classified by magnetic resonance as Pfirrmann grade IV and grade V. Six patients were operated on two levels, resulting in twenty-six intervertebral discs that were submitted to immunohistochemistry to verify the protein expression of autophagy and apoptosis markers. Results: The autophagic markers had greater protein expression in the human intervertebral disc (Pfirrmann Grades IV and V). Under these conditions, autophagy and apoptosis showed a negative correlation. Regarding apoptosis, caspase 8 presented the highest protein expression, which allows inferring the preference for the extrinsic pathway in cell death. Conclusions: Autophagy had the greatest protein expression negative profile compared to apoptosis. Caspase 8 had the highest protein expression in apoptosis.

Towards on the Mediators in Collagen Replacement: Effect of the Active Molecules into a Polymeric Biomaterial

Modulating healing factors could avoid or minimize some possible pathological processes in collagen deposition. The present study was aimed to evaluated the role of active biomolecules such as PDGF-BB and PRP loaded or not into polymeric biomaterial to seek potential mediators in types I and III collagen deposition and epithelization. The healing phases were investigated by using an in vivo full-thickness wound rat model. At zero, 3rd, 7th and 14th days after the experimental model, the size of the wound areas was photographed. The nanofibrous materials were biocompatible and did not cause any local adverse reaction and/or inflammation. On day 14 the wounds had healed almost 100% with better signs of healing, however there was no obvious difference in the wound contraction rates. At the end of 14 days, samples from the center of the lesion were collected when histological features and immunopositivity for collagen I and III expressions were assessed. There was no significant difference in the epithelization among the groups. Wounds treated with PRP and with PA-6/SOMA plus PDGF-BB had significantly lower amounts of type III collagen. The amounts of type I collagen did not have a statistically different deposition among the experimental groups. The association of PDGF-BB with PA-6/SOMA emerges as an alternative for topical application to unfavorable anatomical sites, suggesting that these associations may have a positive modulation on the process of accelerated healing remodeling.

Genotoxicity Clues to Predict Intervertebral Disc Degeneration: A Systematic Review

Objective: To characterize the association between DNA damage and Intervertebral disc degeneration (IDD). Summary of Background Data: IDD is the main disorder causing low back pain and is the most promising target for intervention. Many factors can contribute to the etiology, such as genetics, environment and lifestyle, but it is not yet fully understood. DNA damage can influence this process and needs to be studied, as well as the agents that can determine these damages. Methods: A systematic literature search of PubMed, Web of Science and Scopus was performed to identify studies related to DNA damage to the intervertebral disc. Results: After screening 61 records, 7 articles were included according to the selection criteria. All studies showed some relation between DNA damage and IDD. However, DNA damage was always considered a secondary issue to be investigated. Conclusions: Many factors can influence DNA damage induced by different genotoxic agents on the degenerative cascade of IVD. However, the correlation between IDD severity and DNA damage, as well as the factual role of DNA damage in disc degeneration could not be defined.