Neuron/Glial Antigen 2-Type VI Collagen Interactions During Murine Temporomandibular Joint Osteoarthritis

Abstract

The degeneration of articular cartilage underscores the clinical pathology of temporomandibular joint osteoarthritis (TMJ-OA) and is promoted through dysfunctional biochemical or biophysical signaling. Transduction of these signals has a multifaceted regulation that includes important cell-matrix derived interactions. The matrix encapsulating the cells of the mandibular condylar cartilage (MCC) is rich in type VI collagen. Neuron/glia antigen 2 (NG2) is a type I transmembrane proteoglycan that binds with type VI collagen. This study defines the temporospatial dynamics of NG2-type VI collagen interactions during the progression of TMJ-OA. Membrane-bound NG2 is found to colocalize with pericellular type VI collagen in superficial layer cells in the MCC perichondrium but is present at high levels in the cytosol of chondroblastic and hypertrophic cells. When TMJ -OA is induced using a surgical instability model, localized disruptions of pericellular type VI collagen are observed on the central and medial MCC and are associated with significantly higher levels of cytosolic NG2. NG2 localized within the cytosol is found to be transported through clathrin and dynamin mediated endocytic pathways. These findings are consistent with NG2 behavior in other injury models and underscore the potential of NG2 as an entirely novel molecular mechanism of chondrocyte function contextually linked with TMJ-OA.

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

“…Whole mount immunolabeling of type VI collagen imaged using two-photon fluorescence (TPF) does reconstruct this pericellular matrix in the superficial layer ECM ( Fig 2B ). The general organization of pericellular type VI collagen from TPF matches that observed from confocal immunofluorescence [ 26 , 30 ], with the strongest stain encapsulating the cells and weak staining in the interterritorial matrix between cells. SHG and superficial layer TPF colocalization is weak in non-surgical control MCC ( Fig 2C ).…”

“…Experimental endpoints included four time points: 4, 8, 12, and 16 weeks post-injury. Time points were chosen based on previous descriptions of the mouse model [ 10 , 26 ]. All experiments using vertebrate animals were approved by the University of Illinois at Chicago Animal Care Committee and performed in accordance with the relevant guidelines and regulations.…”

“…Injury to the MCC may activate chondro-progenitor cells in the superficial layer [ 24 , 25 ], particularly from the medial and lateral margins. Type VI collagen binding molecules such as neuron/glial antigen 2 have been shown to internalize at the site of injury during the progression of TMJ OA [ 26 ]. Type VI collagen is a critical molecule for cell migration and proliferation and may be locally expressed to facilitate the migration of these cells in response to injury [ 23 , 27 , 28 ].…”

Temporomandibular Joint Hypofunction Secondary to Unilateral Partial Discectomy Attenuates Degeneration in Murine Mandibular Condylar Cartilage

“…Temporomandibular joint osteoarthritis was induced by unilateral partial discectomy 24,26) . Seven-week-old, male c57 BL/6J mice were anesthetized with ketamine (100 mg/kg) and xylazine (5 mg/kg).…”

Type VI Collagen Regulates Endochondral Ossification in the Temporomandibular Joint

“…A study by Alexopoulos and colleagues ( 6 ) showed that Col6α1 ‐KO mice had accelerated joint degeneration in the femoral head leading to early development of OA as well as delayed ossification. Yotsuya and colleagues ( 45 ) showed changes in the distribution of type VI collagen and Neuron/Glial Antigen 2 (NG2), a cell membrane proteoglycan that binds to type VI collagen, in the TMJ during surgically induced osteoarthritis. The authors suggest that type VI collagen could be mediating cartilage degeneration through interactions with NG2.…”