Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway.

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression.

OBJECTIVE: Disc calcification is strongly associated with disc degeneration; however, the underlying mechanisms driving its pathogenesis are poorly understood. This study aimed to provide a gene expression profile of nucleus pulposus cells (NPCs) from calcified discs, and clarify the potential mechanism in disc degeneration. METHODS: Primary NPCs were isolated from calcified and control discs (CAL-NPC and CON-NPC), respectively. The proliferation and extracellular matrix (ECM) metabolism capacities of the cells were evaluated using MTT and Western blotting, respectively. RNA sequencing was used to identify differentially expressed genes (DEGs) in the CAL-NPCs. The biological functions of the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network. The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated. RESULTS: The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs. In total, 375 DEGs were identified in the CAL-NPCs. The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways. GATA-binding protein 3 (GATA3) with the highest verified levels was selected for further studies. Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function, while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes. CONCLUSION: This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

Ceramic on Ceramic or Ceramic-on-polyethylene for Total Hip Arthroplasty: A Systemic Review and Meta-analysis of Prospective Randomized Studies.

BACKGROUND: Wear debris of polyethylene has become a restraining factor of the durability for total hip arthroplasty (THA). Ceramic on ceramic (COC) has better wear resistance while the squeaking sound and prosthesis fracture are of concern. It is still a controversy that bearing couples are better for THA. METHODS: We performed a systematic review of all English articles identified from PubMed (1966-), Embase (1980-) and the Cochrane Library. Clinical outcomes, complications, revision rates, and radiographic outcomes of COC-THA and ceramic on polyethylene (COP)-THA were compared and evaluated. RESULTS: Eight prospective randomized trials enrolling a total of 1508 patients and 1702 THA surgeries were identified. Our results demonstrated the prosthesis fracture and the squeaking sound is significantly higher in COC group and higher wear rate of the COP. Hip function, loosening rate, dislocation rate, revision rate, and the osteolysis rate were comparable between two groups. According to Grading of Recommendations Assessment, Development and Evaluation system assessment, the strength of evidence was high for prosthesis fracture, dislocation, osteolysis, and moderate for radiolucent line or loosening, hip noise, and revision. CONCLUSIONS: Up to now, there is insufficient evidence to identify any clinical advantage of COC compared with COP. Longer follow-up of larger randomized trial is needed to clarify the outcomes.

Establishment and assessment of rat models of glucocorticoid-induced osteonecrosis.

OBJECTIVE: To establish the rat models of glucocorticoid-induced osteonecrosis and evaluate the osteonecrosis by high-resolution micro-CT and histomorphology. METHODS: Totally 30 Sprague-Dawley male adult rats (age:12 weeks; body weight:400-450 g) were randomized into two groups:one group received two doses of intraperitoneal injection of lipopolysaccharide (20 µg/kg) at an interval of 24 hours, 24 hours later, the rats received three doses of intramuscular injection of methylprednisolone (40 mg/kg) at an interval of 24 hours; in the control group,the rats received same amount of normal saline. Four weeks later, 5 rats in each group were sacrificed randomly.Eight weeks later, all the remaining rats were sacrificed and the femur specimens were scanned by micro-CT. The trabeculae parameters of the femoral head were calculated. The hematoxylin and eosin staining were performed to calculated the success rate. RESULTS: The incidence of osteonecrosis was 80% in the experimental group. The micro-CT demonstrated broken and cystic degeneration. The quantitative analysis showed that the bone volume/total volume (experimental group:0.55 ± 0.13 vs. CONTROL GROUP: 0.68 ± 0.12;P<0.05), bone surface area / bone volume (experimental group:20.45 ± 5.13 vs. CONTROL GROUP: 24.00 ± 5.20;P<0.05), and trabeculae number(experimental group: 5.67 ± 0.50 vs. CONTROL GROUP: 6.24 ± 0.96; P<0.05) were significantly lower in experimental group than those in control group. CONCLUSIONS: A rat model of glucocorticoid-induced osteonecrosis was successfully established by lipopolysaccharide and methylpredniso- lone. High-resolution micro-CT is useful for the qualitative and quantitative analyses of the morphology and structure of trabeculae, showing good consistence with the histomorphological findings.

Anatomy, definition, and treatment of the "terrible triad of the elbow" and contemplation of the rationality of this designation.

In the realm of orthopaedics, the terrible triad of the elbow is infamous, not simply because the prognosis is poor for most patients, but also, maybe to a greater extent, because the unique name of this malady attracts considerable attention and interest in both doctors and patients. The adjective terrible is bestowed on an elbow triad that comprises three coexisting complicated traumas; namely, radial head and ulnar coronoid process fractures and posterior dislocation of the elbow joint. In this review, the classification, treatment principles and prognosis for different forms of management of the radial head and ulnar coronoid process fractures and the ligaments lesions are introduced sequentially and various surgical procedures and their efficacy are discussed. This triad has long given orthopedic surgeons headaches. Nonetheless, in recent years a series of anatomical mechanical studies on the elbow joint have been published and there have been several breakthroughs in surgical techniques for managing this elbow triad. This review examines some memorable millstones and unveils trends in the current clinical norm for this triad. The accomplishments achieved recently have reportedly resulted in enhanced prognoses in the last two or three years compared with previous years. It is therefore high time to revise our thoughts about the justice and accuracy of defining this triad of the elbow as terrible. Lastly, we may safely conclude that the terrible triad of the elbow is much less terrible than previously, provided the commonly approved clinical approaches are undertaken.

[Effects of pedicle subtraction osteotomy on spino-pelvic parameters of ankylosing spondylitis].

OBJECTIVE: Pedicle subtraction osteotomy (PSO) is a spinal realignment technique of correcting the sagittal spinal imbalance. Theoretically, the level and degree of resection via a PSO should impact the degree of sagittal correction. However, the quantitative effect of PSO level and focal angular change on postoperative spino-pelvic parameters has not been fully elucidated. The purpose of this study was to analyze the relationship between the level/degree of PSO and changes in global sagittal balance and spino-pelvic parameters. METHODS: Retrospective analysis was conducted for 34 patients undergoing PSO surgery for ankylosing spondylitis. Preoperative and postoperative free-standing sagittal radiographs were obtained and analyzed by regional curves (lumbar lordosis, thoracic kyphosis), pelvic parameters of pelvic tilt (PT), pelvic incidence (PI) and sacral slope (SS) and global balance of sagittal vertical axis (SVA). And the correlations between PSO parameters (level and degree) and spino-pelvic parameters were analyzed. RESULTS: There were significant changes in spino-pelvic parameters including decreased thoracic kyphosis, increased lumbar lordosis, decreased SVA, decreased PT and increased SS. The decreased SVA were 3.94 ± 3.38 and 3.97 ± 1.91 in lumbar/thoracic osteotomy respectively (P > 0.05). The decreased values of PT were 9.71 ± 6.46 and 5.20 ± 2.74 respectively (P < 0.05). Larger degree of osteotomy (≥ 22°) had greater SVA and PT decreases (P < 0.05). CONCLUSION: PSO is a quite useful technique of restoring spinal alignment. Lumbar and larger degrees of osteotomy have greater effects on spino-pelvic parameters.