Table 1. Proteins associated with mineralization in vertebrates along with their tissue distribution, their effect on mineralization in vitro, and their potential role in vivo.

Protein	Tissue Distribution	Effect in vitro, Adsorbeda,b	Effect in vitro, Dissolvedc	Possible Role in vivo d	Ref.
Aggrecan (proteoglycan)	Cartilage		Inhibitor		[143]-[145]
Albumin	Blood, body fluids, bone	Inhibitor/nucleator; no effect	Inhibitor/nucleator	Inhibitor	This study [2], [62]–[64], [81]–[84], [102]–[112], [146]–[149]
Amelogenin	Enamel, bone, others	No effect	Inhibitor; no effect		[109], [150]–[153]
Biglycan (proteoglycan)	Bone, connective tissues, teeth	Inhibitor/nucleator	Inhibitor		[102], [154]–[159]
Bone acidic glycoprotein-75	Bone, connective tissues, teeth	Nucleator		Nucleator	[142], [160], [161]
Bone sialoprotein	Bone, dentin	Nucleator	Inhibitor; no effect	Nucleator*	[142], [162]–[170]
Chondrocalcin	Cartilage, retina	No effect	No effect		[165]
Collagen type I	Bone, cartilage, dermis, others		No effect	Structure	[99]
Decorin (proteoglycan)	Bone, connective tissues, teeth	Inhibitor/nucleator; no effect	Inhibitor; no effect		[102], [154]–[159]
Dentin matrix protein-1	Bone, dentin, kidney, others	Nucleator		Nucleator*	[142], [148], [171]–[174]
Dentin phosphophoryn	Dentin	Inhibitor/nucleator	Inhibitor	Nucleator	[99], [142], [165], [175]–[178]
Dentin sialoprotein	Dentin	Inhibitor/nucleator		Nucleator	[178], [179]
Fetuin-A (α2-HS-glycoprotein)	Blood, body fluids, bone	No effect	Inhibitor/nucleator	Inhibitor*	This study [2], [56], [57], [66]–[68], [180], [181]
Fibrinogen	Blood	Nucleator	Inhibitor		[104], [110], [182]
Fibronectin	Blood, connective tissues		Inhibitor/nucleator		[106], [107]
Lithostatin	Pancreas, pancreatic secretion		Inhibitor	Inhibitor**	[56], [183]–[185]
Matrix gla protein	Arteries, bone, cartilage			Inhibitor*	[56], [186], [187]
Osteocalcin (bone gla protein)	Blood, bone, cartilage, teeth	Nucleator; no effect	Inhibitor		[102], [165], [188]–[190]
Osteonectin	Bone, dentin, others	Inhibitor/nucleator; no effect	Inhibitor		[165], [191]–[194]
Osteopontin	Arteries, bone, kidney, others	Inhibitor/no effect	Inhibitor	Inhibitor*	[142], [162], [164], [165], [195], [196]
Prothrombin fragment-1	Blood, urine		Inhibitor	Inhibitor***	[197]
Statherin	Saliva		Inhibitor	Inhibitor	[56], [198]–[200]
Tamm-Horsfall protein	Kidney, urine		Inhibitor	Inhibitor***	[201]–[203]
Uropontin	Kidney, urine		Inhibitor	Inhibitor***	[56], [204]
Vitronectin	Blood, bone		Inhibitor/nucleator		[106]

^aThe effect of the proteins on mineralization was studied in vitro following their adsorption onto solid substrates such as agarose beads, agarose gels, or collagen fibrils.

^bThe term “Nucleator” refers to a protein which is able to induce mineral formation in a metastable solution where precipitation does not occur spontaneously. An “Inhibitor” consists of a protein which has the ability to delay or prevent mineral formation.

^cThe effect of various proteins on mineralization was also studied following dissolution of each protein into a liquid buffer.

^dThe word “Structure” refers to a protein which does not appear to induce or inhibit mineral formation by itself, but which is known to be important for the disposition and the arrangement of minerals formed in vivo.

*The potential role of each protein during mineralization in vivo was proposed based on gene deletion studies in laboratory animals when available; in this case, the proteins were denoted with a single asterisk. A role for the other proteins shown was proposed based on limited functional studies giving sometimes divergent results; the role of these proteins should therefore be considered with strong reservation.

**Inhibition of pancreatic stones of calcium carbonate.

***Inhibition of kidney stones of calcium oxalate or calcium phosphate.

This Table was adapted and modified from the review by Benesch et al. [100].