Osteopontin deficiency and aging on nanomechanics of mouse bone

Abstract

Osteoporosis is a bone disease characterized by low bone mass and deterioration of the tissue leading to increased fragility. Osteopontin (OPN), a noncollageneous bone matrix protein, has been shown to play an important role in osteoporosis, bone resorption, and mineralization. However, OPN's role in bone mechanical properties on the submicron scale has not been studied in any detail. In this study, nanoindentation techniques were utilized to investigate how OPN and aging affect bone mechanical properties. Hardness and elastic modulus were calculated and compared between the OPN-deficient mice (OPN(-/-)) and their age and sex-matched wild-type (OPN(+/+)) controls. The results show that the mechanical properties of the young OPN(-/-) bones (age < 12 weeks) are significantly lower than that of the youngest OPN(+/+) bones. This finding was confirmed by additional microindentation testing. Biochemical analysis using micro-Raman spectroscopy indicated more mineral content in young OPN(+/+) bones. Older (age > 12 weeks) bones did not show any significant differences in mechanical properties with genotype. In addition, OPN(+/+) bones show a decrease in mechanical properties between young and older age groups. By contrast, OPN(-/-) bones showed no significant change in mechanical properties with aging.

Load-bearing in cortical bone microstructure: Selective stiffening and heterogeneous strain distribution at the lamellar level

“…In addition to bone mass, factors such as age (Hui et al, 1988;Zioupos and Currey, 1998), disease (Cowin, 2001), and genetic background (Jepsen et al, 2001), affect the fragility of bone, independently of bone mass (Hui et al, 1988;Kanis et al, 2005). This further supports that the extraordinary "material" properties of bone, such as the optimized load transfer and advanced energy dissipation mechanisms (Fantner et al, 2005;Gupta et al, 2006b;Kavukcuoglu et al, 2007), are to be attributed to bone quality.…”

Raman Assessment of Bone Quality

“…Although NCPs in bone are not observed spectroscopically by Raman spectroscopy, their effect on bone composition can be studied by comparing bone tissues from wild-type and knockout animals. For instance, Raman studies show that mineral-to-matrix ratios in osteopontindeficient (OPNÀ/À) mice with ages of 12 weeks or less are lower than in wild type (OPN +/+) mice [35]. Mechanical studies show young OPNÀ/À mice have lower hardness and elastic modulus compared with OPN +/+ mice, confirming osteopontin's role in the early stages of mineralization.…”

Contributions of Raman spectroscopy to the understanding of bone strength

“…47 There are a few studies of the correlation between biomechanical parameters and Raman spectroscopic composition parameters in mouse models of disorders, including osteogenesis imperfect (OI) [48][49][50][51] and osteoporosis, 52 as well as on the effects of knocking out matrix proteinase, 53 transcription factor 54 and noncollagenous proteins. [55][56][57][58][59][60][61][62] These are discussed in the following sections.…”

“…Femurs from fibrillin-2 (Fbn2 À / À ), 55 fetuin-A/alpha-HSglycoprotein (Ahsg À / À ), 59 osteopontin (OPN À / À ) 56 and osteocalcin (OC À / À ) 57 -deficient mice have been studied using bone mechanics and Raman spectroscopy. In one study,…”