Correlating vestibular schwannoma size with vestibular-evoked myogenic potential results.

OBJECTIVES: The maximum size of the vestibular schwannoma (VS) that is compatible with preservation of the function of the vestibular nerve in performing stereotactic radiosurgery remains unclear. This study utilized ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) test results to correlate with the size of VS. DESIGN: Fifty patients with unilateral VS underwent audiometry, and caloric, oVEMP and cVEMP tests. Tumor size from magnetic resonance imaging was measured on the axial plane, and the relationships between tumor size and each test result were analyzed. RESULTS: The pure-tone average from four frequencies did not significantly predict tumor size. Alternatively, oVEMP and cVEMP responses remained significant predictors for tumor size in the regression model, namely, tumor size (cm) = 0.62 × (oVEMP response) + 1.39 × (cVEMP response), where oVEMP and cVEMP responses were regarded as binary variables, in which 1 and 0 reflect abnormal and normal responses, respectively. This model explained 76% of the variance. Accordingly, the estimated VS size exhibiting abnormal oVEMPs and cVEMPs is >2.01 (0.62 +1.39) cm. CONCLUSIONS: When VS size is <2.0 cm, preservation of the function of superior/inferior vestibular nerve indicated by the oVEMP/cVEMP test is achievable. Therefore, both oVEMP and cVEMP tests may serve as supplementary tools for determining treatment option in VS patients.

Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation.

Deficiency of the collagen receptor discoidin domain receptor tyrosine kinase (DDR2) in mice and humans results in dwarfism and short limbs, of which the mechanism remains unknown. Here we report that DDR2 is a key regulator of osteoblast differentiation. DDR2 mRNA expression was increased at an early stage of induced osteoblast differentiation. In the subchondral bone of human osteoarthritic knee, DDR2 was detected in osteoblastic cells. In mouse embryos, DDR2 expression was found from E11 to E15, preceding osteocalcin (OCN) and coinciding with Runx2 expression. Activating transcription factor 4 (ATF4) enhanced DDR2 mRNA expression, and knockdown of ATF4 expression delayed DDR2 induction during osteoblast differentiation. A CCAAT/enhancer binding protein (C/EBP) binding site at -1150 bp in the DDR2 promoter was required for ATF4-mediated DDR2 activation. C/EBPß bound to and cooperated with ATF4 in stimulating DDR2 transcription; accordingly, the ATF4 mutants deficient of C/EBPß binding were incapable of transactivating DDR2. Overexpression of DDR2 increased osteoblast-specific gene expression. Conversely, knockdown of DDR2 suppressed osteogenic marker gene expression and matrix mineralization during the induced osteogenesis. The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters. Together our findings uncover a pathway in which ATF4, by binding to C/EBPß transcriptionally upregulates DDR2 expression, and DDR2, in turn, activates Runx2 through p38 MAPK to promote osteoblast differentiation.