SMAD1 and Leigh syndrome: Consistent with the findings from aged osteoporotic VCF patients, there were comparable Smurf1 expression, but decreased BMP-2 level and elevated Smurf1 activity (Smad1 bound to Smurf1) with large variations in aged osteoporotic LSS patients, when compared to those in adult LDH patients (Fig. 2a and Supplementary Fig. 2a).