Priscila Ladeira Casado

Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives

Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts, chondroblasts, adipocytes, and even myoblasts. Most studies have focused on finding MSCs in different parts of the body for medical treatment. Every joint structure, including bone, joint fat, articular cartilage, and synovium, potentially contains resident MSCs. Recently, a progenitor cell population has been found in synovial fluid and showed similarities with both bone marrow and synovial membrane MSCs. Synovial fluid MSCs have been studied in healthy persons and osteoarthritic patients in order to explore its potential for treatment of some orthopedic disorders. Here, we briefly review the current knowledge on synovial fluid MSCs, their origin, relation to some orthopedic diseases, and future applications.

Identification of periodontal pathogens in healthy periimplant sites.

Purpose:The aim of this study was to evaluate the presence of periodontopathogens in subgingival periimplant sites in partially edentulous patients using polymerase chain reaction procedures, with regard to areas with clinical and radiographic signs of health and areas presenting periimplant disease. Materials and Methods:Thirty nonsmoking, partially edentulous patients, aged 30 to 76 years, were included in this study and divided in 3 groups according their clinical and radiographic characteristics. Group A (n = 10) presented periimplant health, group B (n = 10) presented periimplant mucositis, and group C (n = 10) were patients with periimplantitis. Periimplant tissues were clinically examined as regards the color of mucosae, presence of bacterial plaque, depth and bleeding on probing, and local suppuration. History of periodontal disease was also considered. Radiographic analysis evaluated the presence of bone loss around the implant. Samples of periimplant crevicular fluid were collected to analyze the presence of periodontal pathogens, Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), and Treponema denticola (Td). Results:The results showed that the history of periodontal disease is associated with periimplant disease. The bacteria Aa, Pg, Pi, Td, and Tf were present in periimplant sites clinically and radiographically characterized, as healthy periimplant tissues, mucositis, and periimplantitis. Conclusions:We concluded that Aa, Pg, Pi, Td, and Tf are present in healthy and diseased conditions. Therefore, these periodontal pathogens are not strictly related to periimplant disease sites.

The effect of autologous concentrated bone-marrow grafting on the healing of femoral shaft non-unions after locked intramedullary nailing

The aim of this study was to assess the union rates in a series of patients with failed femoral shaft aseptic non-union who were treated with percutaneous concentrated autologous bone marrow grafting. Bone marrow harvesting and cell injection were performed under general anaesthesia in a single surgical procedure. Radiographic union was diagnosed in fractures with a score ≥ 10 according to the radiographic union scale in tibial fractures (RUST) and confirmed by clinical examination. Eight out of 16 patients progressed to consolidation (RUST score ≥ 10). Radiographic evidence of fracture union was observed at an average of 4.75 ± 1.75 months (range 3 to 8 months). All eight patients who did not progress to union within 12 months following the cell grafting procedure had a RUST score ≤ 10 (range 4 to 9). There were no differences in age, number of previous surgeries, duration of nonunion and preoperative RUST score between the patients that developed solid union and those with failed consolidation. However, a relationship between the number of osteoprogenitors injected and the rate of union was noted, 20.2 ± 8.6 × 10(8) versus 9.8 ± 4.3 × 10(8), p<0.005, between the patients with and without union, respectively. The efficacy of percutaneous autologous concentrated bone marrow grafting seems to be related to the number of osteoprogenitors available in the aspirates. Optimisation of the aspiration technique and concentration process is of paramount importance to increase the incidence of a successful outcome.

Evidence of genetic variations associated with rotator cuff disease.

BACKGROUND Rotator cuff disease (RCD) is a complex process influenced by a multitude of factors, and a number of gene pathways are altered in rotator cuff tears. Polymorphisms in these genes can lead to an extended tendon degeneration process, which explains why subsets of patients are more susceptible to RCD. MATERIALS AND METHODS Twenty-three single-nucleotide polymorphisms within 6 genes involved in repair and degenerative processes (DEFB1, DENND2C, ESRRB, FGF3, FGF10, and FGFR1) were investigated in 410 patients, 203 with a diagnosis of RCD and 207 presenting with absence of RCD. Exclusion criteria were patients older than 60 years and younger than 45 years with a history of trauma, rheumatoid arthritis, autoimmune syndrome, pregnancy, and use of corticosteroids. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped with TaqMan real-time polymerase chain reaction. The χ(2) test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of many covariates and the incidence of RCD. RESULTS Statistical analysis revealed female sex (P = .001; odds ratio, 2.07 [1.30-3.30]) and being white (P = .002; odds ratio, 1.88 [1.21-2.90]) to be risk factors for RCD development. A significant association of haplotypes CCTTCCAG in ESRRB (P = .05), CGACG in FGF3 (P = .01), CC in DEFB1 (P = .03), and FGFR1 rs13317 (P = .02) with RCD could be observed. Also, association between FGF10 rs11750845 (P = .03) and rs1011814 (P = .01) was observed after adjustment by ethnic group and sex. CONCLUSIONS Our work clearly supports the role of DEFB1, ESRRB, FGF3, FGF10, and FGFR1 genes in RCD. Identification of these variants can clarify causal pathways and provide a clue for therapeutic targets.

History of Chronic Periodontitis Is a High Risk Indicator for Peri-Implant Disease

The success rates in implant dentistry vary significantly among patients presenting previous history of periodontitis. The aim of this study was to evaluate if patients with history of chronic periodontitis (CP) are more susceptible to peri-implant disease (PID) than those without history of CP. Two hundred and fifteen individuals, under periodontal maintenance, presenting 754 osseointegrated implants, were selected for this study. The patients were divided into two groups according to the peri-implant status: Control group (patients without PID; n=129) and PID group (patients with PID; n=86). All peri-implant regions were clinically evaluated, including analyses of mucosa inflammation, edema and implant mobility. Periapical radiography assessed the presence of peri-implant bone loss. According to the clinical/radiographic characteristics, patients in Control and PID groups were diagnosed as having CP or not. Nominal variables were evaluated by the chi-square test. The distribution of numeric variables was analyzed by Shapiro-Wilk test. Students t-test and Mann-Whitney test were used to analyze significant differences for parametric and non-parametric data. A p-value <0.05 was considered significant. There was a highly significant correlation between CP history and PID (p<0.0001). Patients with CP had 4 times more chance of developing PID than patients with healthy periodontal tissues. Also, CP patients showed higher bleeding on probing (p=0.002) and bone loss around implant (p=0.004) when compared with patients without CP. In conclusion, history of CP is a high risk factor for the development of PID, irrespective of gender or region of implant placement.

Immediate Dental Implant Failure Associated With Nasopalatine Duct Cyst

This case report presents an analysis of the clinical, radiographic, and histological features of a peri-implant lesion around an implant placed immediately after extraction of a tooth with a periapical lesion. A 52-year-old man received an immediate implant (3.75 × 11.5 mm2) placed in the anterior region of the maxilla. Three years after implant placement, the patient presented with swelling in the anterior portion of the maxilla. Radiographic examination showed a well-circumscribed radiolucency around the implant. The implant and the lesion were removed and fixed in 10% buffered formalin and processed. Histological analysis showed 3 types of epithelium: respiratory, cuboidal, and non-keratinized stratified squamous. In the cyst wall peripheral nerves, arteries, veins, and chronic inflammation were present. The diagnosis was nasopalatine duct cyst. We concluded that the nasopalatine duct cyst can develop in association with dental implants. Clinically, the lesion is similar to the classical nasopalatine duct cyst. Histological analysis should be mandatory in all cases of peri-implant lesions and in all dental periapical lesions before immediate implant placement.

Genome wide association scan for chronic periodontitis implicates novel locus

BackgroundThere is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).MethodsGenotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.ResultsThe rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.ConclusionsOur data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis.

Polymorphisms in BMP4 and FGFR1 genes are associated with fracture non-union

Fracture healing is a complex process influenced by a multitude of factors and expression of several thousand genes. Polymorphisms in these genes can lead to an extended healing process and explain why certain patients are more susceptible to develop non‐union. A total of 16 SNPs within five genes involved in bone repair pathogenesis (FAM5C, BMP4, FGF3, FGF10, and FGFR1) were investigated in 167 patients with long bone fractures, 101 with uneventful healing, and 66 presenting aseptic non‐unions. Exclusion criteria were patients presenting pathological fractures, osteoporosis, hypertrophic and infected non‐unions, pregnancy, and children. All genetic markers were genotyped using TaqMan real‐time PCR. Chi‐square test was used to compare genotypes, allele frequencies, and haplotype differences between groups. Binary logistic regression analyzed the significance of many covariates and the incidence of non‐union. Statistical analysis revealed open fracture to be a risk factor for non‐union development (p < 0.001, OR 3.6 [1.70–7.67]). A significant association of haplotype GTAA in BMP4 (p = 0.01) and FGFR1 rs13317 (p = 0.005) with NU could be observed. Also, uneventful healing showed association with FAM5C rs1342913 (p = 0.04). Our work supported the role of BMP4 and FGFR1 in NU fracture independently of the presence of previously described risk factors.

New strategy to control cell migration and metastasis regulated by CCN2/CTGF

Connective tissue growth factor (CTGF)/CCN family member 2 (CCN2) is a CCN family member of matricellular signaling modulators. It has been shown that CCN2/CTGF mediates cell adhesion, aggregation and migration in a large variety of cell types, including vascular endothelial cells, fibroblasts, epithelial cells, aortic smooth muscle and also pluripotent stem cells. Others matricellular proteins are capable of interacting with CCN2/CTGF to mediate its function. Cell migration is a key feature for tumor cell invasion and metastasis. CCN2/CTGF seems to be a prognostic marker for cancer. In addition, here we intend to discuss recent discoveries and a new strategy to develop therapies against CCN2/CTGF, in order to treat cancer metastasis.

Ridge bone maintenance in human after extraction.

Purpose:The aim of this study was to evaluate, clinically and histologically, the tissues formed in human alveolar sockets filled with bovine morphogenetic protein/bovine organic matrix (BOM) and absorbable membrane (AM) immediately after extraction. Materials:Forty-six human alveolar sockets, exhibiting buccal bone defects were selected for this study. Group 1 received no biomaterial to serve as control. Sockets from group 2 were filled with bovine bone morphogenetic protein (bBMP) associated with bOM. The association of bBMP/bOM/AM filled the alveolar defects from group 3. AM was placed over the defects from group 4. Clinical evaluation analyzed ridge width before biomaterial filling and 4 months after filling. Fifteen specimens were collected from groups 2, 3, and 4 for histologic analyses. Results:Clinical results showed no significant augmentation on the control group (−0.16 ± 0.28 mm). All test sites, groups 2, 3, and 4, showed relevant ridge width augmentation (3.0 ± 0.5 mm, 2.4 ± 0.3 mm, and 2.9 ± 0.6 mm, respectively) and no resorption. Histologically, all experimental alveolar sockets showed active bone formation with osteoid, osteoblasts, and cell differentiation. Conclusion:On the basis of this study, we concluded that bBMP/bOM with or without AM could preserve the ridge showing viable bone formation for future implant placement.