Osteomodulin as a small leucine-rich proteoglycan: Structure-function relationships in extracellular matrix regulation.

Osteomodulin (OMD) is a class II small leucine-rich proteoglycan enriched in mineralized extracellular matrices. This review evaluates OMD-specific evidence linking structural features to matrix interactions and tissue responses. Biochemical and mutational studies support roles in type I collagen recognition and fibril assembly, whereas hydroxyapatite affinity does not establish direct control of mineral nucleation. Cell and animal studies implicate OMD in osteogenic differentiation, osteoclast regulation, and inflammatory responses, but support for individual mechanisms ranges from direct ligand binding to complex association and model-specific perturbation. Findings in vascular, renal, and fibroproliferative models differ across experimental settings, while human expression associations alone do not establish causality. We therefore distinguish experimentally supported activities from model-limited observations and mechanistic hypotheses. Molecular form, post-translational modification, extracellular presentation, and partner availability are plausible determinants of OMD activity, but their causal contributions remain largely untested. Preclinical development will require molecularly defined preparations, pharmacokinetic characterization, and indication-specific delivery strategies.