The Effect of β-Aminopropionitrile on Skeletal Micromorphology and Osteogenesis

Yu Shen; Dian Jing; Jin Hao; Ge Tang; Pu Yang; Zhihe Zhao

doi:10.1007/s00223-018-0430-4

The Effect of β-Aminopropionitrile on Skeletal Micromorphology and Osteogenesis

Calcif Tissue Int. 2018 Oct;103(4):411-421. doi: 10.1007/s00223-018-0430-4. Epub 2018 Jun 18.

Authors

Yu Shen¹, Dian Jing¹, Jin Hao², Ge Tang¹, Pu Yang³, Zhihe Zhao⁴

Affiliations

¹ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, #14, 3rd section of Renmin South Road, Chengdu, 610041, China.
² Harvard School of Dental Medicine, Harvard University, Cambridge, MA, USA.
³ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, #14, 3rd section of Renmin South Road, Chengdu, 610041, China. yangpu@scu.edu.cn.
⁴ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, #14, 3rd section of Renmin South Road, Chengdu, 610041, China. zhzhao@scu.edu.cn.

PMID: 29916126
DOI: 10.1007/s00223-018-0430-4

Abstract

Collagen cross-linking, as a form of collagen post-translational modification, plays a crucial role in maintaining bone mechanical properties as well as in regulating cell biological functions. Shifts in cross-links profile are found apparently correlated to kinds of skeletal pathology and diseases, whereas little is known about the relationship between collagen cross-links and osteogenesis. Here, we hypothesized that the inhibition of collagen cross-links could impair skeletal microstructure and inhibit osteogenesis. A mouse model of collagen cross-linking defects has been established using subcutaneous injection of 350 mg/kg β-aminopropionitrile (BAPN) daily for 4 weeks, and same dose of phosphate buffered saline (PBS) served as control group. The analysis of bone microstructural parameters revealed a significant decrease of bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), and increase of bone surface ratio (BS/BV), structure model index (SMI) as well as trabecular separation (Tb.Sp) in the experimental group (p < 0.05), whereas there was no difference observed in bone mineral density (BMD). Histological staining displayed that the BAPN treatment caused thinner trabeculae and decrease of collagen content in proximal tibiae. The analysis of osteogenesis PCR (Polymerase Chain Reaction) array reflected that BAPN remarkably influenced the expression of Alpl, Bglap, Bgn, Bmp5, Col10a1, Col1a1, Col1a2, Col5a1, Itga2b, and Serpinh1. The results of immunohistochemistry displayed a significant reduction in the mean optical densities of OCN and COL1 at the presence of BAPN. The overall results of this study suggested that BAPN alters bone microstructure and hinders the expression of osteogenic genes without affecting mineralization processes, indicating the influences of collagen cross-links on osteogenesis may be a potential pathological mechanism in skeletal diseases.

Keywords: Bone remodeling; Collagen cross-links; Extracellular matrix (ECM); Osteogenesis; Skeleton micromorphology; β-Aminopropionitrile (BAPN).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminopropionitrile / toxicity*
Animals
Bone and Bones / drug effects
Bone and Bones / pathology*
Collagen / drug effects*
Cross-Linking Reagents / toxicity*
Extracellular Matrix / drug effects
Extracellular Matrix / pathology
Male
Mice
Mice, Inbred C57BL
Osteogenesis / drug effects*

Substances

Cross-Linking Reagents
Aminopropionitrile
Collagen