Two-photon fluorescence and second harmonic generation characterization of extracellular matrix remodeling in post-injury murine temporomandibular joint osteoarthritis.

David A Reed,Mamoru Yotsuya,Peter T Toth,Andrew Bertagna,Polina Gubareva,Esmaiel Jabbari

doi:10.1371/journal.pone.0214072

Abstract

End stage temporomandibular joint osteoarthritis (TMJ-OA) is characterized by fibrillations, fissures, clefts, and erosion of the mandibular condylar cartilage. The goal of this study was to define changes in pericellular and interterritorial delineations of the extracellular matrix (ECM) that occur preceding and concurrent with the development of this end stage degeneration in a murine surgical instability model. Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy was used to evaluate TMJ-OA mediated changes in the ECM. We illustrate that TPF/SHG microscopy reconstructs the three-dimensional network of key fibrillar and micro-fibrillar collagens altered during the progression of TMJ-OA. This method not only generates spatially distinct pericellular and interterritorial delineations of the ECM but distinguishes early and end stage TMJ-OA by signal organization, orientation, and composition. Early stage TMJ-OA at 4- and 8-weeks post-injury is characterized by two structurally distinct regions containing dense, large fiber collagens and superficial, small fiber collagens rich in types I, III, and VI collagen oriented along the mesiodistal axis of the condyle. At 8-weeks post-injury, type VI collagen is locally diminished on the central and medial condyle, but the type I/III rich superficial layer is still present. Twelve- and 16-weeks post-injury mandibular cartilage is characteristic of end-stage disease, with hypocellularity and fibrillations, fissures, and clefts in the articular layer that propagate along the mediolateral axis of the MCC. We hypothesize that the localized depletion of interterritorial and pericellular type VI collagen may signify an early marker for the transition from early to end stage TMJ-OA, influence the injury response of the tissue, and underlie patterns of degeneration that follow attritional modes of failure.

Highlights

Temporomandibular joint osteoarthritis (TMJ-OA) is a clinical syndrome that includes arthralgia, limited joint mobility, and diminished quality of life [1, 2], and is associated with dysfunctional remodeling of the mandibular condylar cartilage (MCC) and degeneration
Extracellular matrix remodeling during early and end stage TMJ-OA alters the orientation of superficial layer collagens
We illustrate that dysfunctional remodeling of the mandibular condylar cartilage (MCC) produces measurable differences in the organization, orientation, and composition of the superficial layer extracellular matrix (ECM) that delineate early and end stage temporomandibular joint osteoarthritis (TMJ-OA)

Summary

Introduction

Temporomandibular joint osteoarthritis (TMJ-OA) is a clinical syndrome that includes arthralgia, limited joint mobility, and diminished quality of life [1, 2], and is associated with dysfunctional remodeling of the mandibular condylar cartilage (MCC) and degeneration. In early stage TMJ-OA, the fibrous layer of the MCC thickens as the articular surface flattens and expands [3, 4]. This fibrous tissue is similar in composition and appearance to granulation tissue [5, 6]. End stage TMJ-OA is the result of unresolved chronic signaled dysfunction and is characterized by hypocellularity, matrix fibrillations, fissures, clefts, and erosion of the MCC. There is a critical need for defining how alterations in pericellular and interterritorial delineations of the ECM distinguish early and end stage TMJ-OA

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