Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied.
In this study, we engineered mesenchymal stem cells (MSCs) to over-express basic fibroblast growth factor (bFGF) and evaluated its effects on fracture healing. Adipose-derived mouse MSCs were transduced to express bFGF and green fluorescence protein (ADSCbFGF-GFP). Closed-femoral fractures were performed with osterix-mCherry reporter mice of both sexes.
MicroRNAs (miRNA) significantly contribute to bone formation by post-transcriptional regulation of gene expression. Mature miRNAs are generated following sequential cleavage by DROSHA/DGCR8 and DICER. However, recent studies have identified that some miRNAs require only one of these enzymes. Most studies seeking to clarify the role of miRNA during bone formation have been performed using DICER deletion strategies, but little is known regarding the role of DGCR8.
Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients.
The coupling of osteoblasts and osteocytes by connexin43 (Cx43) gap junctions permits the sharing of second messengers that coordinate bone cell function and cortical bone acquisition. However, details of how Cx43 converts shared second messengers into signals that converge onto essential osteogenic processes are incomplete. Here, we use in vitro and in vivo methods to show that Cx43 and Runx2 functionally interact to regulate osteoblast gene expression and proliferation, ultimately affecting cortical bone properties.
The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (−/−) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype.