Michaela Kneissel

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Low bone mass and strength lead to fragility fractures, for example, in elderly individuals affected by osteoporosis or children with osteogenesis imperfecta. A decade ago, rare human mutations affecting bone negatively (osteoporosis-pseudoglioma syndrome) or positively (high-bone mass phenotype, sclerosteosis and Van Buchem disease) have been identified(More)
UNLABELLED Expression of the osteocyte-derived bone formation inhibitor sclerostin in adult bone requires a distant enhancer. We show that MEF2 transcription factors control this enhancer and mediate inhibition of sclerostin expression by PTH. INTRODUCTION Sclerostin encoded by the SOST gene is a key regulator of bone formation. Lack of SOST expression is(More)
The runt family transcription factor core-binding factor alpha1 (Cbfa1) is essential for bone formation during development. Surprisingly, transgenic mice overexpressing Cbfa1 under the control of the 2.3-kb collagen type I promoter developed severe osteopenia that increased progressively with age and presented multiple fractures. Analysis of skeletally(More)
Mutations in distant regulatory elements can have a negative impact on human development and health, yet because of the difficulty of detecting these critical sequences, we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients(More)
Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has a unique structure with two catalytic domains and a domain binding ubiquitin with high affinity. This enzyme was recently identified as a multisubstrate protein deacetylase that can(More)
Beta-Catenin-dependent canonical Wnt signaling plays an important role in bone metabolism by controlling differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. To investigate its function in osteocytes, the cell type constituting the majority of bone cells, we generated osteocyte-specific beta-catenin-deficient mice (Ctnnb1(loxP/loxP);(More)
Excess of Vitamin A (retinol) and related compounds (retinoids) induces bone fragility and is associated with increased hip fracture incidence in humans. Yet, their impact on the adult skeleton has been studied in relatively little detail. It is assumed that they induce generalized bone loss and decrease long-bone thickness due to reduction of radial bone(More)
The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-alpha is implicated in bone metabolism. We studied the effect of ERRalpha silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERRalpha silencing led to an increase of bone sialoprotein and a decrease of osteopontin mRNA levels, suggesting(More)
Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing and 2-month-old Sost deficient male mice and(More)