osteoprotegerin and Ankylosis

This study aimed to investigate genetic variations in the osteoprotegerin-encoding gene (TNFRSF11B) in patients with temporomandibular joint ankylosis (TMJA).. The sample comprised 17 patients diagnosed with TMJA, of both sexes with ages ranging from 6 to 57 years old. TNFRSF11B mutational analysis was performed using the Sanger sequencing method with DNA extracted from oral cells, and the functional impact prediction of the variants was assessed using bioinformatic analysis.. Sequencing analysis identified 15 (88.23%) patients that presented at least 1 genetic variant in TNFRSF11B. The mutation rs202090603 (p.E33K) was found in 6 individuals, and rs140782326 (p.V281M), rs11573942 (p.L295), and rs1375250340 (p.I389T) were identified in 1 subject each. According to the pathogenicity potential of mutations, 3 variants were considered of low impact (rs2073618, rs202090603, and rs2228568) and 3 as disease causing (rs140782326, rs11573942, and rs1375250340). The variant rs202090603 (p.E33K) was found in the first cysteine domain with differences in the loop positions of p.E33K mutated the 3D structure of osteoprotegerin.. Two polymorphisms (rs2073618 and rs2228568) and the mutations rs202090603 (p.E33K), rs140782326 (p.V281M), rs11573942 (p.L295), and rs1375250340 (p.I389T) in the TNFRSF11B gene may be associated with TMJA.

Topics: Adolescent; Adult; Ankylosis; Child; Female; Humans; Male; Middle Aged; Mutation; Osteoprotegerin; Temporomandibular Joint; Temporomandibular Joint Disorders; Young Adult

To evaluate the association between polymorphisms in genes that regulate bone metabolism, such as OPG, RANK, RANKL, and HIF1A, in patients with temporomandibular joint (TMJ) ankylosis.. The sample consisted of 181 individuals, the study included 17 individuals with TMJ ankylosis and 164 controls. DNA was extracted from buccal epithelial cells. The genotyping of genetic polymorphisms in OPG (rs2073618), RANK (rs3826620), RANKL (rs9594738), and HIF1A (rs2301113 and rs2057482) was performed by real-time PCR using TaqMan™ technology (Applied Biosystems). The data were subjected to statistical analysis with a level of significance of 0.05.. The OPG (rs2073618) polymorphism was associated with TMJ ankylosis, both in the additive model and in the dominant model (p < 0.05). In the additive model, when the individuals carried the CC genotype, they presented as 10.80 times more likely to develop the condition (p = 0.03). In the dominant model, individuals that carried at least one C allele were 5.76 times more likely to have TMJ ankylosis, than those with the G allele (p = 0.01).. The polymorphism rs2073618 of OPG is a possible marker that is associated with the risk of manifestation of TMJ ankylosis.

Topics: Ankylosis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Osteoprotegerin; Patients; Polymorphism, Single Nucleotide; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Temporomandibular Joint; Temporomandibular Joint Disorders

Otosclerosis is an inflammatory disease associated with persistent measles virus (MV) infection of the otic capsule. The nature of sensorineural hearing loss (SNHL) related to otosclerosis can be due to the chronic TNF-alpha release from the foci. TNF-alpha enters the inner ear fluid spaces in histologically active stages of otosclerosis and may cause outer hair cell functional disorder and subsequent SNHL without morphological changes of the organ of Corti. On the contrary, non-otosclerotic stapes ankylosis being a non-inflammatory disease is not harmful for hair cells. Theoretically, SNHL should not associate to this type of stapes fixation. Stapes footplates (N = 248) were examined by hematoxylin-eosin staining and corresponding MV-, OPG- and TNF-alpha-specific RT-PCR. Anti-measles IgG levels of serum specimens were measured by ELISA. Preoperative audiological results were correlated with otosclerotic and non-otosclerotic histopathologies. Among patients with stapes fixation, we found 93 active and 67 inactive otosclerosis, and 88 non-otosclerotic stapes ankylosis. MV could only be detected in otosclerotic stapes footplates. Audiometry revealed bone conduction threshold elevation toward the high frequencies in otosclerotic patients, which was associated to the duration of hearing loss. OPG mRNA expression was significantly lower in the TNF-alpha positive specimens, which was independent from virus positivity. In about one-third of stapes fixations, the etiology is non-otosclerotic stapes ankylosis. Histologic otosclerosis exhibits a strong correlation with MV presence in the bone as a sign of persistent MV infection and related inflammation with TNF-alpha release. This causes SNHL in the function of time. Non-otosclerotic stapes fixations do not cause high-frequency SNHL.

Topics: Adult; Aged; Ankylosis; Case-Control Studies; Female; Hearing Loss, Sensorineural; Humans; Male; Measles; Measles virus; Middle Aged; Osteoprotegerin; Otosclerosis; RNA, Messenger; RNA, Viral; Stapes; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Osteoprotegerin inhibits osteoclastogenesis and plays an important role in the control of bone resorption. However, the genetic mechanisms underlying regulation of OPG levels are currently not fully elucidated. The aim of the present study was to determine whether the ANKH gene, which plays a central role in bone mineralization, contributes to the genetic regulation of OPG levels. A family-based association study used a sample of 159 ethnically homogeneous nuclear families, comprising 556 apparently healthy individuals. Statistical analyses included family aggregation analysis of OPG variation and four types of transmission disequilibrium tests. Each individual was genotyped for 11 SNPs in the ANKH gene. Four TDTs consistently showed a highly significant association between OPG levels and the intronic SNP rs875525 located between exons 6 and 7. The combined p-value for four tests to reject the null hypothesis of no association was 0.0003. Furthermore, haplotypes generated between rs875525 and two additional neighbouring SNPs (rs2291943 and rs2288474) also revealed a significant association with OPG plasma levels (p < 10(-4)-10(-3)). ANKH genetic polymorphisms in the area between SNP rs2291943 and rs2288474 are strongly associated with OPG plasma levels. The molecular mechanism underlying this association is not obvious, and therefore these results should be regarded cautiously until they are confirmed in independent studies.

Topics: Adult; Aged; Animals; Ankylosis; Bone Remodeling; Ethnicity; Female; Haplotypes; Humans; Male; Membrane Proteins; Mice; Middle Aged; Osteoprotegerin; Phosphate Transport Proteins; Polymorphism, Single Nucleotide; Russia