Perturbed Collagen Differentially Alters Mineral Between Craniofacial and Axial Bones

Objectives: Bone is a composite, primarily composed of collagen, mineral, and proteins. Systemic conditions (e.g., diabetes, rheumatoid arthritis) exhibit altered composition leading to structural and mechanical changes. These changes are often site dependent (i.e., craniofacial bones versus axial bones), and associated with altered turnover rates and collagen composition. Our hypothesis is that alterations to collagen via perturbations in cross-linking alters mineral and mechanics differentially, dependent on mineral apposition rate (MAR).
Methods: Collagen cross-links were perturbed with an established model using b-aminoproprionitrile (BAPN) in growing, 5 week-old male C57BL/6 mice. Femora (n=5-7) and mandibles (n=8) from mice treated with 350 mg/kg BAPN or control for 3 weeks. Dynamic histomorphometry was performed to determine the MAR in the growing femur cortex and trabeculae, and mandibular cortical and interradicular bone. Nanoindentation and Raman spectroscopy was performed for mechanical properties, as well as mineral quantity and composition, respectively.
Results: BAPN treatment showed increased mineral crystallinity in the femur and mandibular cortical bone (low MAR), as well as interradicular bone (high MAR) (p<0.05) and a decrease in the femur trabeculae (high MAR) (p<0.05). Mineral carbonate/phosphate was increased in cortex of the mandible and femur and decreased in the femur trabeculae (p<0.05). BAPN treatment impaired mechanical properties in the mandible cortex with high MAR, and low carbonate/phosphate.
Conclusions: In our model of perturbed collagen, mineral crystallinity is regulated differently in the mandible versus the femur. The femur has compartment and MAR dependent changes to mineral crystallinity and carbonate/phosphate. The mandible shows increased crystallinity and carbonate/phosphate with perturbed collagen (MAR independent) and reduced mechanical properties in the cortex (lowest MAR). Therefore, collagen cross-link perturbation has a negative functional effect in the mandibular cortex. Crystallinity and carbonate/phosphate are also altered with cross-link changes, but they are differentially regulated between axial (MAR dependent) and craniofacial bones (MAR independent).