A preliminary analysis of the wear pathways of sliding contacts on temporomandibular joint total joint replacement prostheses

In the last years, several materials and design have been assessed in an attempt to improve the mechanical performance of temporomandibular joint total joint replacement (TMJ TJR) prostheses. However, the wear of the TMJ TJR condyle to the polymer-based fossa component during loading and sliding movements. That promotes the release of debris and risks of toxicity to the surrounding tissues. The purpose of this study was to perform a narrative literature review on the wear of TMJ TJR sliding contacts and potential toxicity of metallic debris to the patients. Previous studies reported a significant deterioration of the sliding contact surfaces of TMJ TJR prostheses. Material loss as a result of wear can cause a TMJ TJR condyle/fossa mismatch and the modification of the contact pressure and chewing loading. As a further consequence of wear, metal particles are released to the surrounding tissues with a high risk of local tissue and systemic toxicity through the bloodstream. The presence of particles induces the stimulation of inflammatory reactions depending on the concentration and size of debris. Thus, CoCr-based condyle release metallic ions and sub-micron particles that can be engulfed by macrophages or internalized by other tissue cells. The wear and material loss of TMJ TJR could be decreased by design optimization and novel materials with low friction and contact pressure. That consequently decrease the amount of metallic ions and particles to the surrounding tissues, preventing peri-prosthetic inflammatory reactions.This study was supported by FCT-Portugal (UID/EEA/04436/2013, NORTE-01-0145- FEDER-000018—HAMaBICo, POCI-01-0145-FEDER-031035_LaserMULTICER), SFRH/BPD/123769/ 2016 and CNPq-Brazil (CNPq/UNIVERSAL/421229/2018-7)

Identification of Regions Involved in Substrate Binding and Dimer Stabilization within the Central Domains of Yeast Hsp40 Sis1

Protein folding, refolding and degradation are essential for cellular life and are regulated by protein homeostatic processes such those that involve the molecular chaperone DnaK/Hsp70 and its co-chaperone DnaJ. Hsp70 action is initiated when proteins from the DnaJ family bind an unfolded protein for delivery purposes. In eukaryotes, the DnaJ family can be divided into two main groups, Type I and Type II, represented by yeast cytosolic Ydj1 and Sis1, respectively. Although sharing some unique features both members of the DnaJ family, Ydj1 and Sis1 are structurally and functionally distinct as deemed by previous studies, including the observation that their central domains carry the structural and functional information even in switched chimeras. In this study, we combined several biophysical tools for evaluating the stability of Sis1 and mutants that had the central domains (named Gly/Met rich domain and C-terminal Domain I) deleted or switched to those of Ydj1 to gain insight into the role of these regions in the structure and function of Sis1. The mutants retained some functions similar to full length wild-type Sis1, however they were defective in others. We found that: 1) Sis1 unfolds in at least two steps as follows: folded dimer to partially folded monomer and then to an unfolded monomer. 2) The Gly/Met rich domain had intrinsically disordered characteristics and its deletion had no effect on the conformational stability of the protein. 3) The deletion of the C-terminal Domain I perturbed the stability of the dimer. 4) Exchanging the central domains perturbed the conformational stability of the protein. Altogether, our results suggest the existence of two similar subdomains in the C-terminal domain of DnaJ that could be important for stabilizing each other in order to maintain a folded substrate-binding site as well as the dimeric state of the protein.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Ministerio da Ciencia e Tecnologia/Conselho Nacional de Pesquisa e Desenvolvimento (MCT/CNPq