Investigating the Role of Lysine Post-Translational Modifications in Type I Collagen for Bone Mineralization (2024)
Undergraduate: Matthew Mills
Faculty Advisor: Mitsuo Yamauchi
Department: Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry
Lysyl hydroxylase 2 (LH2) is a member of the LH enzyme family that catalyzes the hydroxylation of telopeptidyl lysine (Lys) residues on type I collagen for cross-link formation. Varying functions of this particular isozyme have been found to yield significant bone-related disease such as Bruck syndrome, a recessive osteogenesis imperfecta. While the importance of LH2 on bone diseases has been studied, little work has been done to understand how LH2 impacts bone mineralization. To investigate this, we modulated LH2 activity in vitro across four osteoblastic cell culture conditions and assessed their extent of mineralization and cross-linking products formed by conducting a mineralization assay and cross-link analysis. Cross-link analysis revealed that cultures containing the LH2 activator contained significantly more hydroxylysine-aldehyde (Hylald) derived cross-links with concomitant decreases in Lysald-derived cross-links. Equally, the mineralization assay displayed statistically significant differences in mineralization profiles across culture conditions. This data underscores that LH2 activity creates a significant impact on the post-translational profiles and cross-linking products of type I collagen, and these differences may impact the extent to which bone mineralization occurs. Continued study of these relationships in conjunction with more mature cell cultures could reveal significant insights on how LH2 creates mineralization changes over time to yield differing bone functionalities.