TY - JOUR
T1 - Hypermineralization of Hearing-Related Bones by a Specific Osteoblast Subtype
AU - Kuroda, Yukiko
AU - Kawaai, Katsuhiro
AU - Hatano, Naoya
AU - Wu, Yanlin
AU - Takano, Hidekazu
AU - Momose, Atsushi
AU - Ishimoto, Takuya
AU - Nakano, Takayoshi
AU - Roschger, Paul
AU - Blouin, Stéphane
AU - Matsuo, Koichi
N1 - Funding Information:
This work was supported by JSPS KAKENHI grant numbers 17H04015 to KM, 16 K08506 and 19 K07256 to YK, and the Keio University Academic Development Fund, and in part by the Network Joint Research Center for Materials and Devices (proposal numbers 20201125, 20183033, and 20173037). Synchrotron experiments were performed with approval of the SPring‐8 committee (proposal numbers 2016B1043, 2017A1195, 2017B1284, and 2018B1216). The system of synchrotron radiation X‐ray phase imaging was developed with the support of JST ERATO grant number JPMJER1403 to AM. This study was supported by the AUVA (Austrian Social Insurance for Occupational Risk) and the OEGK (Austrian Health Insurance Fund).
Funding Information:
We thank Karol Vegso and Koh Hashimoto for help with X-ray phase imaging; Norio Amizuka for the ALP antibody; Toshihiro Nagai for help with TEM imaging; Ayako Sakamoto, Kazumasa Takenouchi, and other staff at Collaborative Research Resources at Keio University School of Medicine for technical help; Ryota Tamura for artwork; and Elise Lamar and Masaki Yoda for critical reading of the manuscript. The authors also thank Petra Keplinger, Sonja Lueger, and Phaedra Messmer for sample preparation and qBEI measurements at the bone material laboratory at the Ludwig Boltzmann Institute of Osteology, Vienna, Austria. This work was supported by JSPS KAKENHI grant numbers 17H04015 to KM, 16 K08506 and 19 K07256 to YK, and the Keio University Academic Development Fund, and in part by the Network Joint Research Center for Materials and Devices (proposal numbers 20201125, 20183033, and 20173037). Synchrotron experiments were performed with approval of the SPring-8 committee (proposal numbers 2016B1043, 2017A1195, 2017B1284, and 2018B1216). The system of synchrotron radiation X-ray phase imaging was developed with the support of JST ERATO grant number JPMJER1403 to AM. This study was supported by the AUVA (Austrian Social Insurance for Occupational Risk) and the OEGK (Austrian Health Insurance Fund). Authors? roles: YK, KK, and KM devised the experimental strategy, analyzed data, and prepared the manuscript. YK performed histological, biochemical, and genetic experiments. NH performed and analyzed mass spectrometry data. YW, HT, KM, and AM performed and analyzed synchrotron radiation X-ray phase imaging. TI and TN performed and analyzed microbeam X-ray diffraction imaging. SB performed CLSM imaging. SB and PR evaluated qBEI results and combined them with CLSM data. All authors approved the manuscript. Author contributions: YK: Conceptualization; data curation; formal analysis; investigation; methodology; writing-original draft; writing-review & editing. KK: Conceptualization; validation; writing-review & editing. NH: Investigation; methodology. YW: Investigation; methodology. HT: Investigation; methodology. AM: Investigation; methodology. TI: Investigation; methodology. TN: Investigation; methodology. PR: Investigation; methodology. SB: Investigation; methodology. KM: Conceptualization; data curation; formal analysis; funding acquisition; investigation; methodology; project administration; supervision; validation; visualization; writing-original draft; writing-review & editing.
Publisher Copyright:
© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
PY - 2021/8
Y1 - 2021/8
N2 - Auditory ossicles in the middle ear and bony labyrinth of the inner ear are highly mineralized in adult mammals. Cellular mechanisms underlying formation of dense bone during development are unknown. Here, we found that osteoblast-like cells synthesizing highly mineralized hearing-related bones produce both type I and type II collagens as the bone matrix, while conventional osteoblasts and chondrocytes primarily produce type I and type II collagens, respectively. Furthermore, these osteoblast-like cells were not labeled in a “conventional osteoblast”-specific green fluorescent protein (GFP) mouse line. Type II collagen-producing osteoblast-like cells were not chondrocytes as they express osteocalcin, localize along alizarin-labeled osteoid, and form osteocyte lacunae and canaliculi, as do conventional osteoblasts. Auditory ossicles and the bony labyrinth exhibit not only higher bone matrix mineralization but also a higher degree of apatite orientation than do long bones. Therefore, we conclude that these type II collagen-producing hypermineralizing osteoblasts (termed here auditory osteoblasts) represent a new osteoblast subtype.
AB - Auditory ossicles in the middle ear and bony labyrinth of the inner ear are highly mineralized in adult mammals. Cellular mechanisms underlying formation of dense bone during development are unknown. Here, we found that osteoblast-like cells synthesizing highly mineralized hearing-related bones produce both type I and type II collagens as the bone matrix, while conventional osteoblasts and chondrocytes primarily produce type I and type II collagens, respectively. Furthermore, these osteoblast-like cells were not labeled in a “conventional osteoblast”-specific green fluorescent protein (GFP) mouse line. Type II collagen-producing osteoblast-like cells were not chondrocytes as they express osteocalcin, localize along alizarin-labeled osteoid, and form osteocyte lacunae and canaliculi, as do conventional osteoblasts. Auditory ossicles and the bony labyrinth exhibit not only higher bone matrix mineralization but also a higher degree of apatite orientation than do long bones. Therefore, we conclude that these type II collagen-producing hypermineralizing osteoblasts (termed here auditory osteoblasts) represent a new osteoblast subtype.
KW - ANALYSIS/QUANTITATION OF BONE
KW - BONE MATRIX
KW - BONE MODELING AND REMODELING
KW - BONE QCT/MICROCT
KW - CELLS OF BONE
KW - DEVELOPMENTAL MODELING
KW - GENETIC ANIMAL MODELS
KW - MATRIX MINERALIZATION
KW - OSTEOBLASTS
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U2 - 10.1002/jbmr.4320
DO - 10.1002/jbmr.4320
M3 - Article
C2 - 33905562
AN - SCOPUS:85105724290
SN - 0884-0431
VL - 36
SP - 1535
EP - 1547
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 8
ER -