Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations.

ABSTRACT: Bruck syndrome (BS) is a congenital disorder characterized by joint flexion contractures, skeletal dysplasia, and increased bone fragility, which overlaps clinically with osteogenesis imperfecta (OI). On a genetic level, BS is caused by biallelic mutations in either FKBP10 or PLOD2. PLOD2 encodes the lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of cross-linking lysine residues in fibrillar collagen telopeptide domains. This modification enables collagen to form chemically stable (permanent) intermolecular cross-links in the extracellular matrix. Normal bone collagen develops a unique mix of such stable and labile lysyl-oxidase-mediated cross-links, which contribute to bone strength, resistance to microdamage, and crack propagation, as we

SUBMITTER: Gistelinck C 

PROVIDER: S-EPMC7990156 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature