METHODS: Bone mineral was assessed using x-ray diffraction (XRD), microhardness and backscattered electron imaging (BSE). Bone collagen was assessed using α-chymotrypsin digestion, differential scanning calorimetry (DSC), gel electrophoresis (SDS-PAGE) and polarized light microscopy (PLM).

RESULTS: BSE, microhardness and XRD revealed no changes in bone mineral due to KOH treatment. DSC showed an altered curve shape (lower and broader), indicating a change in collagen organization due to KOH treatment. Decreased α-chain band intensity in 14-day KOH treated groups detected using SDS-PAGE indicated α-chain fragmentation due to KOH treatment. PLM images revealed differences in collagen structure in terms of pattern distribution of preferentially oriented collagen between the periosteal and endocortical regions.

CONCLUSION: These results suggest that endocortical KOH treatment causes in situ collagen degradation, which explains the previously reported altered mechanical properties.

GENERAL SIGNIFICANCE: Compromising the organic component of bone contributes to an increase in bone fragility.

CLINICAL PROBLEM ADDRESSED: Controlling myofibroblast differentiation and persistence is crucial for developing anti-fibrotic therapies targeting SSc.

BASIC SCIENCE ADVANCES: Insights have been recently generated into how the proteins transforming growth factor beta (TGFbeta), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) contribute to myofibroblast differentiation and pericyte recruitment in general and to the persistent myofibroblast phenotype of lesional SSc fibroblast, specifically.

RELEVANCE TO CLINICAL CARE: This minireview summarizes recent findings pertinent to the origin of myofibroblasts in SSc and how this knowledge might be used to control the fibrosis in this disease.

CONCLUSIONS: TGFbeta, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFbeta, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc.

STUDY DESIGN: One hundred thirty-one approximal surfaces were examined by 2 observers with visual inspection (VI) using the International Caries Detection and Assessment System, radiographic interpretation, and clinically using the Diagnodent pen (LFpen). To achieve a reference standard, surfaces were directly examined for the presence of white spots or cavitations, and lesion depth was determined after sectioning. The area under the receiver operating characteristic curve (A(z)), sensitivity, specificity, and accuracy were calculated, as well as the interexaminer reproducibility.

RESULTS: Using the cavitation threshold, all methods presented similar sensitivities. Higher A(z) values were achieved with VI at white spot threshold, and VI and LFpen had higher A(z) values at cavitation threshold. VI presented higher accuracy and A(z) than radiographic and LFpen at both enamel and dentin depth thresholds. Higher reliability values were achieved with VI.

CONCLUSIONS: VI performs better, but both radiographic and LFpen methods also show good performance in detecting more advanced approximal caries lesions.