Toward the Understanding of Small Protein-Mediated
Collagen Intrafibrillar Mineralization
Posted on 2020-06-25 - 17:20
The design of improved
materials for orthopedic implants and bone
tissue engineering scaffolds relies on materials mimicking the properties
of bone. Calcium phosphate (Ca-PO4)-mineralized collagen
fibrils arranged in a characteristic hierarchical structure constitute
the building blocks of mineralized vertebrate tissues and control
their biomechanical and biochemical properties. Large, flexible, acidic
noncollagenous proteins (ANCPs) have been shown to influence collagen
mineralization but little is known about mineralization mechanisms
with the aid of small proteins. Osteocalcin (OCN) is a small, highly
structured biomolecule known as a multifunctional hormone in its undercarboxylated
form. Here, we examined the potential mechanism of collagen intrafibrillar
mineralization in vitro mediated by OCN as a model
protein. Rapid and random extrafibrillar mineralization of flakey
Ca-PO4 particles was observed by transmission electron
microscopy mainly on the outer surfaces of collagen fibrils of a preformed
collagen scaffold in the absence of the protein. In contrast, the
protein stabilized hydrated, spherical nanoclusters of Ca-PO4 on the outer surface of the fibrils, thereby retarding extrafibrillar
mineralization. The nanoclusters then infiltrated the fibrils resulting
in intrafibrillar mineralization with HAP crystals aligned with the
fibrils. This mechanism is similar to that observed for unstructured
ANCPs. Results of fibrillogenesis and immunogold labeling studies
showed that OCN was associated primarily with the fibrils, consistent
with ex vivo studies on mineralizing turkey tendon.
The present findings contribute to expanding our understanding of
collagen intrafibrillar mineralization and provide insight into design
synthetic macromolecular matrices for orthopedic implants and bone
regeneration.
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Wang, Ziqiu; Ustriyana, Putu; Chen, Kexun; Zhao, Weilong; Xu, Zhijun; Sahai, Nita (2020). Toward the Understanding of Small Protein-Mediated
Collagen Intrafibrillar Mineralization. ACS Publications. Collection. https://doi.org/10.1021/acsbiomaterials.0c00386
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AUTHORS (6)
ZW
Ziqiu Wang
PU
Putu Ustriyana
KC
Kexun Chen
WZ
Weilong Zhao
ZX
Zhijun Xu
NS
Nita Sahai
KEYWORDS
preformed collagen scaffoldacidic noncollagenous proteinsHAPflakey Ca-PO 4 particlescollagen fibrilsSmall Protein-Mediated Collagen Intrafibrillar MineralizationOCNbone tissue engineering scaffoldstransmission electron microscopycollagen intrafibrillar mineralizationmechanisminfluence collagen mineralizationmineralizing turkey tendonANCPextrafibrillar mineralization