The role of amino acids in hydroxyapatite mineralization

Abstract

Polar and charged amino acids (AAs) are heavily expressed in noncollagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca 2þ and PO 4 32 ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca 2þ and PO 4 32 ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves.

Self‐assembling polymeric dendritic peptide as functional osteogenic matrix for periodontal regeneration scaffolds—an in vitro study

“…Upon induction of osteogenic differentiation, the hPDL cells on Lys‐PDA matrix showed early mineralization (Figures and ). Lysine can augment the nucleation and precipitation of hydroxyapatite (HA), the bone mineral component, due to the electrostatic interactions and its affinity to HA . In this study also, an improved mineralization was evident in both alizarin red staining and alizarin red assay, and Von Kossa staining, for calcium and phosphate components of HA, respectively (Figures and ).…”

“…Based on these facts, we chose lysine amino acid to generate the dendritic polydiacetylene matrix. We envisaged that terminal positively charged amino groups of lysine can interact with negatively charged glycosaminoglycan (GAG) receptors on the cell membrane to enhance cell adhesion and facilitate the deposition of phosphate ions to promote biomineralization …”

“…We envisaged that terminal positively charged amino groups of lysine can interact with negatively charged glycosaminoglycan (GAG) receptors on the cell membrane to enhance cell adhesion and facilitate the deposition of phosphate ions to promote biomineralization. [18][19][20][21][22][23] The dendritic polymer Lys-PDA was designed and tested in vitro for cellular responses using human periodontal ligament (hPDL) cells.…”

Matrix vesicles from chondrocytes and osteoblasts: Their biogenesis, properties, functions and biomimetic models

“…Apatite in a crystalline phase is induced by a nucleation step, even if it is generated from ACP. The nucleation can be induced without MVs in vitro by chemical agents such as citrate [110, 111], dimethyl sulfoxide [112] and other natural pro-nucleation agents such as positively charged amino acids [113], aspartic acid [113, 114], acidic carboxyproteins and phosphoproteins [115–117], bone sialioprotein [118], proteins of the enamel matrix (ameloblastin, amelogenin, dentin sialophosphoprotein, enamelin, tuftelin) [119] and hydrophobic fusion protein [120]. However, the contribution of these proteins in mineralization in vivo is highly hypothetical.…”

“…Taken together, these facts indicate that MVs are involved with the initiation of the mineralization process [10] in an efficient manner. At least in vitro , other types of vesicles [98], including unidentified types of vesicles [133], intracellular vesicles [98] or natural pro-nucleating agents [113–120] as well as necrotic cells and cellular remnants [98] may also contribute to the mineralization process. All these patterns of mineralization are the result of different activities of one cell type [98].…”