PubMed · 12612574
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Schubert Charlotte. 2003. Mend the gap.. https://doi.org/10.1038/nm0303-267
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Bone, and especially the subchondral bone plate, is involved in the pathogenesis of osteoarthritis (OA). OA bone tissue is sclerotic yet undermineralized indicating abnormal bone cell metabolism. Studies in both human and animal models of OA support the concept that bone sclerosis could precede cartilage degradation and loss. Clinical studies show that the indices of bone resorption and formation are increased in OA patients. A working hypothesis of the sequence of changes leading to OA holds that enhanced bone remodeling is the initiating event triggering cartilage damage. The attempt to repair the damaged cartilage then leads to a number of biochemical adaptations in bone and cartilage. In bone, this repair attempt modifies insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs), and transforming growth factor-beta (TGF-beta), and alters the urokinase plasminogen activator (uPA)/plasmin system. In the cartilage, it also modifies IGF-1/IGFBP levels and the uPA/plasmin system. However, bone changes may overwhelm the attempts to repair cartilage, and lead to further sclerosis and damage. Some of these specific pathways have been investigated, and indeed are modified in OA subchondral osteoblasts. Thus, subchondral bone sclerosis in OA may be due to abnormal osteoblasts characterized by increased metabolic activities that result in an increase in osteoid matrix that is undermineralized. The exact role played by cytokines and prostaglandins remains controversial. However, restraining collagen deposition and mineral removal, and/or improving mineral deposition, could provide a better, more mineralized, bone matrix in OA patients.
This paper reports on some theoretical work which used fracture mechanics concepts to draw conclusions about the nature of the so-called 'cellular transducer': the means by which bone cells detect the presence of damage and thus initiate remodelling and adaptation activities. Using analytical and numerical methods, we estimated the strains and displacements around cracks of the typical size, shape and orientation that normally occur in compact bone. We predicted that it is not possible for osteocytes or their processes to be fractured as a result of direct tensile strains, because the strains generated are much less than the expected failure strains of cellular material. We proposed a new failure mechanism by which osteocyte processes spanning the crack are cut by shearing motions between the crack faces. We predicted that failures of this type can occur. Failures begin to occur if crack lengths become greater than normal (100 microm), so this could act as a signal to initiate repair processes for individual cracks. Very large numbers of cell processes (greater than 1000) will fail if the crack length and/or applied stress reach dangerous levels (300 microm and 60 Mpa, respectively) at which point bone deposition may be required to prevent stress fractures. Similar results also occurred if we proposed a different mechanism of damage detection, involving cells' ability to detect the high levels of strain that occur near crack tips. This work, though based on theoretical mechanics considerations, suggests some biological experiments which might confirm our findings.