Biomineralization of bone: a fresh view of the roles of non-collagenous proteins

Abstract

The impact of genetics has dramatically affected our understanding of the functions of non-collagenous proteins. Specifically, mutations and knockouts have defined their cellular spectrum of actions. However, the biochemical mechanisms mediated by non-collagenous proteins in biomineralization remain elusive. It is likely that this understanding will require more focused functional testing at the protein, cell, and tissue level. Although initially viewed as rather redundant and static acidic calcium binding proteins, it is now clear that non-collagenous proteins in mineralizing tissues represent diverse entities capable of forming multiple protein-protein nteractions which act in positive and negative ways to regulate the process of bone mineralization. Several new examples from the author’s laboratory are provided which illustrate this theme including an apparent activating effect of hydroxyapatite crystals on metalloproteinases. This review emphasizes the view that secreted non-collagenous proteins in mineralizing bone actively participate in the mineralization process and ultimately control where and how much mineral crystal is deposited, as well as determining the quality and biomechanical properties of the mineralized matrix produced.

Dual Role of the Trps1 Transcription Factor in Dentin Mineralization

“…Mineralization is an orchestrated process in which crystals of calcium phosphate, termed hydroxyapatite (HA), 2 are laid down in precise amounts within the fibrous extracellular matrix (ECM) (1). Physiological mineralization occurs in skeletal tissues (bone and hypertrophic cartilage) and dental tissues (dentin, cementum, and enamel).…”

Clinical Concepts in Oral and Maxillofacial Surgery and Novel Findings to the Field of Bone Regeneration

“…The process by which nucleation is initiated is a constant source of debate and include biomineralization foci, calcospherulites and matrix vesicles. Matrix vesicles have long been contested as sites of nucleation in bone and recent data suggested that the vesicles are present in bone but that they vary in size and the composition (Gorski, 2011). Vesicles have also been shown to be present within biomineralization foci (Huffman et al, 2007).…”

The influence of hydrostatic pressure on tissue engineered bone development

“…Osteoblasts secrete large amounts of specialised extracellular matrix known as osteoid, composed largely of type I collagen. As the cells and the matrix both mature, the secreted proteome changes to include molecules with adaptations for mineralising and structurally modifying the matrix, including alkaline phosphatase, osteocalcin, osteopontin and osteonectin (Gorski, 2011). The presence of these proteins in the extracellular matrix promotes the crystallisation of calcium and phosphate in the interstitial fluid into a basic form of hydroxyapatite aligned with the collagen fibrils, resulting in it becoming increasingly ossified, a process often termed primary mineralisation (Buehler, 2007;Boivin, 2007).…”