Abstract
Understanding the properties of bone is of both fundamental and clinical relevance. The basis of bone’s quality and mechanical resilience lies in its nanoscale building blocks (i.e., mineral, collagen, non-collagenous proteins, and water) and their complex interactions across length scales. Although the structure–mechanical property relationship in healthy bone tissue is relatively well characterized, not much is known about the molecular-level origin of impaired mechanics and higher fracture risks in skeletal disorders such as osteoporosis or Paget’s disease. Alterations in the ultrastructure, chemistry, and nano-/micromechanics of bone tissue in such a diverse group of diseased states have only been briefly explored. Recent research is uncovering the effects of several non-collagenous bone matrix proteins, whose deficiencies or mutations are, to some extent, implicated in bone diseases, on bone matrix quality and mechanics. Herein, we review existing studies on ultrastructural imaging—with a focus on electron microscopy—and chemical, mechanical analysis of pathological bone tissues. The nanometric details offered by these reports, from studying knockout mice models to characterizing exact disease phenotypes, can provide key insights into various bone pathologies and facilitate the development of new treatments.
Highlights
Another possibility is that the deficit in one non-collagenous proteins (NCPs) can alter the expression and/or the distribution pattern of other non-collagenous bone matrix proteins [54,58,79]; identifying their exact roles would require examining a number of knockout animals
This review examined existing studies on the ultrastructural imaging of bone tissues in their pathological states, correlating to their compromised mechanical performance where appropriate
Non-collagenous bone matrix proteins are a vital part of bone, performing both structural and physiological functions
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The structural and mechanical characteristics of pathological bone tissues are discussed in relation to their healthy counterparts, highlighting the importance of ultrastructural imaging and analysis as well as the outstanding challenges in understanding bone diseases at the nanoscale. OC and OPN, in the form of a protein complex, regulate the formation of “dilatational bands” (v100 nm) between mineral aggregates in collagen fibrils when loaded in tension This translates to a dissipation in energy, thereby imparting fracture toughness—that is, the ability of bone to resist fracture during initiation or propagation of a crack through the specimen—to bone at the nanoscale (Figure 2e) [60,70]. This study does shed light on the structural role of the NCPs on bone strength
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