Lubricin is a secreted, cytoprotective
glycoprotein that contributes to the essential boundary lubrication mechanisms necessary for maintaining low friction levels at articular cartilage surfaces. Diminishment of
lubricin function is thereby implicated as an adverse contributing factor in degenerative
joint diseases such as
osteoarthritis.
Lubricin occurs as a soluble component of synovial fluid, and is synthesized and localized in the superficial layer of articular cartilage (and thus has also been described as "superficial zone
protein", or SZP); however, defined interactions responsible for
lubricin retention at this site are not well characterized. In the current studies, we identified molecular determinants that enable
lubricin to effectively bind to articular cartilage surfaces. Efficient and specific binding to the superficial zone was observed for synovial
lubricin, as well as for recombinant full-length
lubricin and a
protein construct comprising the
lubricin C-terminal (
hemopexin-like) domain (LUB-C, encoded by exons 7-12). A construct representing the N-terminal region of
lubricin (LUB-N, encoded by exons 2-5) exhibited no appreciable cartilage-binding ability, but displayed the capacity to dimerize, and thus potentially influence
lubricin aggregation.
Disulfide bond disruption significantly attenuated recombinant
lubricin and LUB-C binding to cartilage surfaces, demonstrating a requirement for
protein secondary structure in facilitating the appropriate localization of
lubricin at relevant tissue interfaces. These findings help identify additional key attributes contributing to
lubricin functionality, which would be expected to be instrumental in maintaining joint homeostasis.