Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called bone resorption) and new bone tissue is formed (a process called ossification or new bone formation). These processes also control the reshaping or replacement of bone following injuries like fractures but also micro-damage, which occurs during normal activity. Remodeling responds also to functional demands of the mechanical loading and inactivity or lack of loading (like with immobilized patients or in zero gravity in space) can lead to extensive bone loss.
An imbalance in the regulation of bone remodeling can result from an imbalance in two sub-processes, bone resorption and bone formation, and can result in many metabolic bone diseases, such as osteoporosis.
[Wikipedia]
SEM sheet of new bone forming
©David Gregory & Debbie Marshall
Bone is in a constant state of remodelling, being turned over, resorbed (by osteoclasts), and regenerated (by osteoblasts). these processes are mediated by cells that dissolve bone, osteoclasts, and cells that make bone, osteoblasts. Both of these have a common parent or progenitor cell called mesenchymal stem cells which can be found in the bone marrow. Mesenchymal stem cells are builder cells, constantly renewing tissues such as hair, skin, nails, bone.
Stem cells, respond to chemical signals that stimulate and guide their maturation into different cell types. Our drug contains EP4a, a potent chemical signal that guides mesenchymal stem cells to mature into osteoblasts. EP4a was originally developed at Merck and has a very well characterized profile. However and despite the fact that effective drugs like this exist, pharmacological barriers and side effects make treating bone diseases difficult.
Mesenchymal stem cell, SEM
Normal bone architecture
SEM of subchondral bone, full thickness
Osteoporotic bone architecture
SEM osteoporotic bone
