Quantitative analysis of the elastic fibres in the human temporomandibular articular disc and its attachments.

A quantitative study of the elastic fibres found in the human temporomandibular disc and its attachments was performed. Seven left discs from 57- to 82-year-old subjects, without macroscopic evidence of a TMJ disorder, were analysed and prepared in parasagittal sections. The surface amount was measured, thresholded and expressed from 0 to 1, using microscopic digitized views after Weigert's resorcin-fuchsin staining of elastic fibres. Fibre density rates ranged from 0 to 0.687. The mean density was 0.1532 (sigma=0.1150) in the upper bilaminary zone, 0.1097 (sigma=0.1159) in the lower bilaminary zone, 0.0474 (sigma=0.0782) in the anterior band, 0.0180 (sigma=0.0603) in the posterior band and null in the intermediate zone. The difference in density rate between the structures was significant, except for the posterior band and the intermediate zone. The elastic fibre density rates in central and medial locations of the upper and lower bilaminary zones were twice as big as in the lateral locations. In the anterior band, the elastic fibre density was less abundant medially than in its lateral part. These quantitative results support the current elastic fibre distribution scheme, and confirm the necessity of studying their orientation, taking into account age and temporomandibular joint health parameters.

Interleukin-6-induced proliferation of pre-B cells mediated by receptor complexes lacking the SHP2/SOCS3 recruitment sites revisited.

Interleukin-6 (IL-6) induces B-cell proliferation by binding to receptor complexes composed of a specific alpha-receptor (gp80; CD126) and the signal transducing receptor subunit gp130 (CD130). Immediately after receptor complex activation, signal transducers and activators of transcription (STATs) 1 and 3 and the Src-homology domain-containing protein tyrosine phosphatase 2 (SHP2) are recruited to gp130 and subsequently tyrosine phosphorylated. The activated dimerized STATs translocate to the nucleus and bind to enhancer elements of IL-6-inducible genes. SHP2 acts as an adapter and links the Jak/STAT pathway to the Ras/Raf/MAPK cascade but it is also involved in signal attenuation. Whereas STAT3 activation appears to be crucial for all biological activities of IL-6, the requirement of SHP2-activation depends on the individual biological response analyzed. The requirement of SHP2 activation for the pre-B cell (Ba/F3) proliferation has been reported previously [Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K. & Hirano, T. (1996) Immunity 5, 449-460]. In contrast, we have recently demonstrated that the presence of a single STAT-recruitment site within gp130 is sufficient for IL-6- induced proliferation of Ba/F3 cells [Schmitz, J., Dahmen, H., Grimm, C., Gendo, C., Müller-Newen, G., Heinrich, P.C. & Schaper, F. (2000) J. Immunol. 164, 848-854]. To unravel this discrepancy we analyzed the IL-6-induced dose-dependent proliferation of Ba/F3 cells mediated by receptor complexes lacking SHP2/SOCS3 recruitment sites. Surprisingly, pre-B cells, after stimulation with low amounts of IL-6, proliferate much more efficiently in the absence of the activated SHP2 than in the presence of the tyrosine phosphatase. Therefore, SHP2 activation appears to be relevant for IL-6-induced proliferation only after stimulation with very large amounts of IL-6.

Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation.

Stimulation of the IL-6R complex leads to Src homology domain containing tyrosine phosphatase 2 (SHP2) recruitment to the receptor subunit gp130 and its subsequent tyrosine phosphorylation. SHP2 is a two-SH2 domain-containing protein tyrosine phosphatase that is activated by many cytokines and growth factors. SHP2 counteracts the activation of transcription factors of the STAT family and the induction of IL-6-responsive genes. Tyrosine 759 of gp130, the signal transducing subunit of the IL-6R complex, is essential for the phosphorylation of SHP2. Mutation of tyrosine 759 to phenylalanine leads to an enhanced inducibility of IL-6-dependent genes. Here we demonstrate that no further tyrosines in the cytoplasmic part of gp130 are required for the phosphorylation of SHP2. We also tested whether the tyrosine 759 motifs in both subunits of the gp130 dimer are required for SHP2 association and tyrosine phosphorylation. Interestingly, one SHP2-recruiting phosphotyrosine motif in a single chain of the gp130 dimer is sufficient to mediate SHP2 association to the gp130 receptor subunit and its tyrosine phosphorylation as well as to attenuate IL-6-dependent gene induction. Furthermore, we show that repression of gene induction via Y759 does not require the presence of the SHP2 and STAT recruitment sites within the same receptor subunit, but within the same receptor complex. The Y759 motif in gp130 also attenuates gene induction mediated by the oncostatin M and leukemia inhibitory factor receptor complexes, which both contain gp130 as the shared subunit.

SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130.

Interleukin-6 is involved in the regulation of many biological activities such as gene expression, cell proliferation, and differentiation. The control of the termination of cytokine signaling is as important as the regulation of initiation of signal transduction pathways. Three families of proteins involved in the down-regulation of cytokine signaling have been described recently: (i) SH2 domain-containing protein-tyrosine phosphatases (SHP), (ii) suppressors of cytokine signaling (SOCS), and (iii) protein inhibitors of activated STATs (PIAS). We have analyzed the interplay of two inhibitors in the signal transduction pathway of interleukin-6 and demonstrate that the tyrosine phosphatase SHP2 and SOCS3 do not act independently but are functionally linked. The activation of one inhibitor modulates the activity of the other; Inhibition of SHP2 activation leads to increased SOCS3-mRNA levels, whereas increased expression of SOCS3 results in a reduction of SHP2 phosphorylation after activation of the interleukin-6 signal transduction pathway. Furthermore, we show that tyrosine 759 in gp130 is essential for both SHP2 and SOCS3 but not for SOCS1 to exert their inhibitory activities on interleukin-6 signal transduction. Besides SHP2, SOCS3 also interacts with the Tyr(P)-759 peptide of gp130. Taken together, our results suggest differences in the function of SOCS1 and SOCS3 and a link between SHP2 and SOCS3.

[The development of craniomandibular disorders after bilateral sagittal osteotomy]. / Evolution des désordres cranio-mandibulaires après une ostéotomie bilatérale sagittale.

The aim of this study is to know the repercussions of modified sagittal ramus split osteotomy of the mandible on the anamnesic symptoms of cranio-mandibular disorders in 89 patients. The sample was divided into different groups according to the surgery type: mandibular advancement or mandibular retrusion with or without maxillary surgery. The anamnesic approach allows to evaluate the felt symptoms. All had a surgery by the same surgeon and with the same technique: mandibular sagittal bilateral surgery according to the modificated Obwegeser osteotomy. The statistical analysis shows some differences between groups.

Oral health in adolescents from a small French town.

In France, caries are more prevalent in rural areas than in large cities. This study analyzed the relationship between number of oral health indices and some known risk factors (toothbrushing, sugar consumption, saliva components) and sociodemographic factors in adolescents from a small town. The sample included 112 children aged 12-14 in the north-east of France. School marks was found to be better linked with dental caries indices than the socio-occupational category of parents: gingival index (GI), DMFS, DMFT and caries severity (CS) significantly increased with decreasing school marks; oral plaque was related to socio-occupational of parents. The analysis using the regression method showed that the variance explained by the various factors studied was modest (between 23 and 30%) for GI, initial caries sites (IS), DS, DMFS, DMFT and CS, and was small for plaque (5%) and calculus (3%). This would be due in part to the wide dispersion of these indices. The sex had a non-significant regression coefficient for all oral health indices investigated. For GI, only mutans streptococci (MS) and plaque had a significant regression coefficient. Calculus was explained by any factor considered. Only MS had a significant part in plaque. IS was explained by MS, toothbrushing and age. For DS, only toothbrushing, MS and sweet drinks during meals had a significant part. DMFS and DMFT were explained only by MS and age. CS was explained by MS, age, salivary buffer pH, salivary flow rate, and toothbrushing.

[The dental health of the children of Lorraine and Haute-Saône in 1987]. / La santé dentaire des enfants Lorraine et de Haute-Saône en 1987.

The oral health of a representative sample of 964 schoolchildren aged 6 to 15 years from primary schools and secondary teaching colleges of Lorraine and Haute-Saône were examined. The gingival, plaque and calculus indices as well as the DMFT, DMFS, dft and dfs, indices were used. A standardized presentation of the results allowed comparisons with other similar surveys. The DMFT of 12 year old children was 3,82 slightly lower than the national mean value. Comparison of caries indices of permanent teeth according to sex showed girls to have a higher prevalence than boys of similar age. Children from rural zones were more affected by caries than those of urban origin.