TY - JOUR
T1 - Distinct Morphologies of Bone Apatite Clusters in Endochondral and Intramembranous Ossification
AU - Hara, Emilio Satoshi
AU - Nagaoka, Noriyuki
AU - Okada, Masahiro
AU - Nakano, Takayoshi
AU - Matsumoto, Takuya
N1 - Funding Information:
The authors thank Dr. Yosuke Kunitomi for his help in the analysis of calvarial bone development. The authors also thank the Central Research Laboratory, Okayama University Medical School, where fluorescence and electron microscopes were available. This study was supported by JSPS KAKENHI Grant Numbers JP18H05254, JP19H03837, JP20H04534, and JP22H03274. The XRD experiment using SmartLab was performed at the Joint Research Center for Environmentally Conscious Technologies in Materials Science (Grant No. JPMXP0621467974) at ZAIKEN, Waseda University.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022
Y1 - 2022
N2 - Bone apatite crystals grow in clusters, but the microstructure of these clusters is unknown. This study compares the structural and compositional differences between bone apatite clusters formed in intramembranous (IO) and endochondral ossification (EO). Calvaria (IO) and femurs (EO) are isolated from mice at embryonic days (E) 14.5 to 15.5 and post-natal days (P) 6 to 7, respectively. Results show that the initially formed bone apatite clusters in EO (≅1.2 µm2) are >10 times larger than those in IO (≅0.1 µm2), without significant changes in ion composition. In IO (E14.5 calvarium), early minerals are formed inside matrix vesicles (MVs). In contrast, in EO (P6 femur epiphysis), no MVs are observed, and chondrocyte-derived plasma membrane nanofragments (PMNFs) are the nucleation site for mineralization. Apatite cluster size difference is linked with the different nucleation sites. Moreover, an alkaline pH and slow P supply into a Ca-rich microenvironment are suggested to facilitate apatite cluster growth, as demonstrated in a biomimetic mineralization system. Together, the results reveal for the first time the distinct and exquisite microstructures of bone apatite clusters in IO and EO, and provide insightful inspirations for the design of more efficient materials for bone tissue engineering and repair.
AB - Bone apatite crystals grow in clusters, but the microstructure of these clusters is unknown. This study compares the structural and compositional differences between bone apatite clusters formed in intramembranous (IO) and endochondral ossification (EO). Calvaria (IO) and femurs (EO) are isolated from mice at embryonic days (E) 14.5 to 15.5 and post-natal days (P) 6 to 7, respectively. Results show that the initially formed bone apatite clusters in EO (≅1.2 µm2) are >10 times larger than those in IO (≅0.1 µm2), without significant changes in ion composition. In IO (E14.5 calvarium), early minerals are formed inside matrix vesicles (MVs). In contrast, in EO (P6 femur epiphysis), no MVs are observed, and chondrocyte-derived plasma membrane nanofragments (PMNFs) are the nucleation site for mineralization. Apatite cluster size difference is linked with the different nucleation sites. Moreover, an alkaline pH and slow P supply into a Ca-rich microenvironment are suggested to facilitate apatite cluster growth, as demonstrated in a biomimetic mineralization system. Together, the results reveal for the first time the distinct and exquisite microstructures of bone apatite clusters in IO and EO, and provide insightful inspirations for the design of more efficient materials for bone tissue engineering and repair.
KW - biomineralization
KW - bone apatite
KW - bone callus
KW - bone defects
KW - endochondral ossification
KW - intramembranous ossification
UR - http://www.scopus.com/inward/record.url?scp=85135053085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85135053085&partnerID=8YFLogxK
U2 - 10.1002/adbi.202200076
DO - 10.1002/adbi.202200076
M3 - Article
C2 - 35859256
AN - SCOPUS:85135053085
SN - 2701-0198
JO - Advanced Biology
JF - Advanced Biology
ER -