Using Cell and Organ Culture Models to Analyze Responses of Bone Cells to Mechanical Stimulation.

The techniques that are useful for applying mechanical strain to bone and bone cells are now more diverse than described in the second Edition. Their output has also increased substantially and, perhaps most importantly, their significance is now broadly accepted. This growth in the use of methods for applying mechanical strain to bone and its constituent cells and increased awareness of the importance of the mechanical environment in controlling normal bone cell behavior has indeed heralded new therapeutic approaches. We have expanded the text to include additions and modifications made to the straining apparatus and updated the research cited to support this growing role of cell cultures, including co-culture systems and primary cells, tissue engineering, and organ culture models to analyze responses of bone cells to mechanical stimulation. We understand that there are approaches not covered here and appreciate that alternative strategies have their own value and utility.

The Chondro-Osseous Continuum: Is It Possible to Unlock the Potential Assigned Within?

Endochondral ossification (EO), by which long bones of the axial skeleton form, is a tightly regulated process involving chondrocyte maturation with successive stages of proliferation, maturation, and hypertrophy, accompanied by cartilage matrix synthesis, calcification, and angiogenesis, followed by osteoblast-mediated ossification. This developmental sequence reappears during fracture repair and in osteoarthritic etiopathology. These similarities suggest that EO, and the cells involved, are of great clinical importance for bone regeneration as it could provide novel targeted approaches to increase specific signaling to promote fracture healing, and if regulated appropriately in the treatment of osteoarthritis. The long-held accepted dogma states that hypertrophic chondrocytes are terminally differentiated and will eventually undergo apoptosis. In this mini review, we will explore recent evidence from experiments that revisit the idea that hypertrophic chondrocytes have pluripotent capacity and may instead transdifferentiate into a specific sub-population of osteoblast cells. There are multiple lines of evidence, including our own, showing that local, selective alterations in cartilage extracellular matrix (ECM) remodeling also indelibly alter bone quality. This would be consistent with the hypothesis that osteoblast behavior in long bones is regulated by a combination of their lineage origins and the epigenetic effects of chondrocyte-derived ECM which they encounter during their recruitment. Further exploration of these processes could help to unlock potential novel targets for bone repair and regeneration and in the treatment of osteoarthritis.