SPARC Regulates Collagen Fibers and Monocyte Activity in Periodontal Disease

Objectives: The periodontal ligament (PDL) is a fibrous connective tissue anchoring tooth into alveolar bone. Collagen type I is the main structural component of the PDL. High rates of extracellular matrix (ECM) turnover are characteristic of PDL tissue. Periodontal disease (PD) afflicts approximately 50% of the adult population (>35 years) in the United States. PD is marked by chronic inflammation of the periodontium leading to PDL degradation, alveolar bone loss, and eventual tooth loss. There are currently no accepted methodologies to regenerate collagenous PDL tissue. Thus PDL provides an excellent tissue milieu for investigating mechanisms of collagen processing and assembly during clinically relevant inflammatory states.
Methods: SPARC, a collagen-binding protein, has been identified as a key factor in collagen ECM deposition. We reported significantly less total collagen, thinner fibers, and reduced mechanical strength in SPARC-null PDL compared to wild type (WT) PDL. A key factor in incorporating and stabilization of mature collagen within the ECM is mediated through collagen cross-linking. Transglutaminases (TGs) are a family of extracellular proteins known to participate in collagen cross-linking activity.
Results: Previous data implicate SPARC as a critical regulator of TG activity on collagen I in homeostatic PDL. The mechanism by which cross-links influence ECM environment, collagen architecture and repair, during and following inflammatory injury is unknown. We hypothesize that increases in tissue TG (TG2) activity in response to injury diminishes collagen fiber content and mechanical strength in the PDL altering the structural environment of the ECM to affect host monocyte response. We will investigate our hypothesis to elucidate mechanistic roles of SPARC in inflammatory cell recruitment, collagen turnover in bone and PDL, and TG2-mediated cross-links.
Conclusions: These studies will provide novel insight into the role of the ECM in the inflammatory response of periodontal disease.