Bone is a dynamic organ system exhibiting continual remodeling. These processes are dependent on the metabolic activity of bone cells: osteoblasts form bone, osteocytes maintain bone, and osteoclasts resorb bone.
Nearly all bone diseases, or pathologies in fracture healing, manifest aberrations in bone matrix production and/or mineralization. Cytokines and hormones tightly regulate these cellular activities in bone, in both normal and pathologic states. Parathyroid hormone (PTH) is a major regulator of bone formation, remodeling and fracture healing. Its endocrine function in vivo is to maintain Ca2+ levels in the blood by reabsorbing renal Ca2+ and releasing Ca2+ from bones.
As a therapeutic agent, PTH also manifests somatotrophic effects on bone formation and is an anabolic agent for reversing bone loss and treating osteoporosis fractures. It is now being tested whether it can be used to augment long bone fracture healing after trauma.
Our basic science research principally investigates bone formation and the regulation of osteoblast function using both cell culture and animal model approaches. Our translational science research focuses on the effects of metabolic bone disease such as osteoporosis on the process of bone formation. Another translational science focus investigates the effects of mechanical unloading (simulated weightlessness) on the process of fracture healing. Our aim is to define the molecular mechanisms operating in the adaptive responses resulting from these biological challenges. This research will advance our knowledge of bone growth and repair and may offer new strategies for treating bone disorders.
Mammals use an internal skeleton for tissue anchoring, weight bearing support, internal organ protection, and storage of calcium and is the main location housing red blood cell production. Our adult skeleton is completely renewed every 10 years without loss of any of these functions. It is no wonder that alterations in our skeleton resulting from aging, disease or trauma result in major medical symptoms and loss of quality of life. My research program aims to uncover novel aspects of how bone tissues form, grow and repair. With such new pre-clinical information, it is hoped that new diagnostic or therapeutic procedures will be built on these principles to improve disorders of metabolic bone disease or fracture healing.
Androjna C, McCabe NP, Cavanagh PR, Midura RJ., Effects of Spaceflight and Skeletal Unloading on Bone Fracture Healing. Clinic Rev Bone Miner Metab. 2011; DOI 10.1007/s12018-011-9080-z
Gorski JP, Huffman NT, Chittur S, Midura RJ, Black C, Oxford J, Seidah NG., Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization. J Biol Chem. 2011 Jan 21;286(3):1836-49.
Wen D, Androjna C, Vasanji A, Belovich J, Midura RJ., Lipids and collagen matrix restrict the hydraulic permeability within the porous compartment of adult cortical bone. Ann Biomed Eng. 2010 Mar;38(3):558-69.
Schnoke M, Midura SB, Midura RJ. Parathyroid hormone suppresses osteoblast apoptosis by augmenting DNA repair. Bone. 2009 Sep;45(3):590-602.
Lerner Research Institute
Mail Code NB21
9500 Euclid Avenue
Cleveland, Ohio 44195