Methionine restriction alters bone morphology and affects osteoblast differentiation

Area of Science:

• Gerontology
• Nutritional Science
• Skeletal Biology

Background:

• Methionine restriction (MR) is known to extend lifespan across various species.
• MR has been shown to influence overall growth in rodents.

Purpose of the Study:

• To investigate the effects of MR on bone structure in young and aged male and female C57BL/6J mice.
• To determine if observed changes in bone parameters are due to MR itself or secondary to body weight reduction.

Main Methods:

• Comparison of bone structure (vBMD, BMC, microarchitecture) between MR and control-fed (CF) mice of different ages and sexes.
• Nanoindentation for intrinsic strength assessment.
• Analysis of plasma biomarkers (leptin, IGF-1, adiponectin, FGF21) and gene expression in preosteoblast cells.

Main Results:

• MR affected growth rates in males and young females, but not aged females.
• MR reduced bone mass and microarchitecture in males and young females, but these changes were attenuated or reversed when adjusted for body weight.
• Intrinsic bone strength was similar between MR and CF groups.
• Plasma biomarkers suggested increased collagen degradation, potentially influenced by hormonal changes.
• In vitro studies showed attenuated gene expression related to collagen formation and osteoblast differentiation under MR conditions.

Conclusions:

• MR alters bone morphology, potentially through delayed osteoblast differentiation.
• The observed reduction in bone mass and microarchitecture in MR mice is largely appropriate for their reduced body size.
• MR does not appear to compromise intrinsic bone strength despite changes in bone morphology.