Searchable abstracts of presentations at key conferences on calcified tissues

ba0005oc2.5 | Bone mass and bone strength Wnt signalling | ECTS2016

Is circulating sclerostin an endocrine modulator of bone mass?

Kulkarni Rishikesh , Schindeler Aaron , Croucher Peter , Little David , Baldock Paul

Mechanosenstitive osteocytes in bone supress the local production of sclerostin in response to mechanical loading, to increase osteoblast differentiation and bone mass. In addition, sclerostin is secreted from osteocytes into the circulation. Serum sclerostin has been shown to correlate with osteoporosis and low bone mass, however there is limited evidence by which to determine whether serum sclerostin is acting either a biomark...

ba0001pp166 | Cell biology: osteoblasts and bone formation | ECTS2013

Activated protein C increases osteoblast proliferation and BMP2 induced bone formation

Shen Kaitlin , Schindeler Aaron J , Cheng Tegan L , Xue Meilang , Little David G , Jackson Chris J

Introduction: Activated protein C (APC) plays an important role in the cutaneous healing of chronic wounds arising from orthopaedic surgery and has cytoprotective and anti-inflammatory properties which may also assist bone repair. The aim of this study was to examine whether APC could directly influence osteoblasts and increase bone formation in a rodent model.Methods: Proliferation of MG-63 osteoblast-like cells was quantified by MTT assay and direct co...

ba0004oc8 | (1) | ICCBH2015

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta

Munns Craig , Peacock Lauren , Mikulec Kathy , Kneissel Michaela , Kramer Ina , Cheng Tegan , Schindeler Aaron , Little David

Introduction: Bisphosphonate treatment in children with osteogenesis imperfecta reduces bone catabolism and relies on modelling to form new bone. An anabolic treatment, anti-sclerostin antibody (Anti-SOST Ab), is being investigated in clinical trials. We hypothesized that combined treatment may produce superior outcomes in OI.Methods: Female Col1a2 G610C mice and their wild type littermates (WT) were treated from week 5 to week 9 of life with either sali...

ba0007oc11 | (1) | ICCBH2019

Targeting adeno-associated viral vectors to fractures and the skeleton

Lee Lucinda , Peacock Lauren , Lisowski Leszek , Little David , Munns Craig , Schindeler Aaron

Objectives: While local gene therapy for bone applications has shown some success in preclinical models, systemic delivery of transgenes to the skeleton remains a considerable challenge. Viral vectors such as adeno-associated viruses (AAVs) have great potential as vectors for systemic transgene delivery and may be adapted for emerging gene editing technologies. Furthermore, AAV vectors can have high efficiency, low immunogenicity, and selective tropism towards different tissue...

ba0001pp60 | Bone development/growth and fracture repair | ECTS2013

MEK inhibitors in fracture healing and NF1 pseudarthrosis

Little David , El-Hoss Jad , Kollind Mille , Deo Nikita , McDonald Michelle , Sullivan Kate , Little Chris , Schindeler Aaron

Neurofibromatosis type 1 (NF1) is a genetic disorder with an incidence of 1/3000. Inactivating mutations in the NF1 gene cause Ras-MEK overstimulation, and predisposes NF1 patients to cancer. A new generation of MEK inhibitors (PD0325901 and AZD6244) are under clinical trials in cancer patients, including NF1 patients. Congenital pseudarthrosis of the tibia is a major complication for NF1 patients, and associates with loss-of-heterozygosity of the NF1 gene. The primary aim of ...