Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity ^1,2,3. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Up-regulation of specific microRNAs has been identified in-vivo in osteoporotic patients ^4,5. It is hypothesized that modulation of specific microRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease.

We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential up-regulation of osteoblastogenesis without cessation of osteoclast activity.

The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on microRNA targeting.

The development of improved therapies for osteoporosis is of great significance due to the predicted rise in incidence of the disease and associated fragility fractures. Targeted therapies, such as the manipulation of microRNA expression, offer the opportunity to increase osteoblastogenesis and decrease osteoclastogenesis, potentially without the associated side effects of older, systemic therapies. We believe our 3D human bone marrow derived osteoporotic model offers the closest relation to the in-vivo environment for assessment and manipulation of microRNA expression.

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Upregulation of specific microRNAs has been identified in-vivo in osteoporotic patients. It is hypothesized that modulation of specific mircoRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease.

We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential upregulation of osteoblastogenesis without cessation of osteoclast activity.

The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on miRNA targeting.

Background

Aseptic loosening remains the primary reason for failure of orthopaedic implants. Therefore a prime focus of Orthopaedic research is to improve osteointegration and outcomes of joint replacements. The topography of a material surface has been shown to alter cell adhesion, proliferation and growth. The use of nanotopography to promote cell adhesion and bone formation is hoped to improve osteointegration and outcomes of implants. We have previously shown that 15nm high features are bioactive. The arrangement of nanofeatures has been shown to be of importance and block-copolymer separation allows nanopillars to be anodised into the titania layer, providing a compromise of control of order and height of nanopillars. Osteoblast/osteoclast stem cell co-cultures are believed to give the most accurate representation of the in vivo environment, allowing assessment of bone remodelling related to biomaterials.