Dataset Information

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

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.

SUBMITTER: Reed DA

PROVIDER: S-EPMC6428409 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Reed David A DA Yotsuya Mamoru M Gubareva Polina P Toth Peter T PT Bertagna Andrew A

PloS one 20190321 3

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 ...[more]

PMID: 30897138

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Project description:The temporomandibular joint (TMJ) disc is a fibrocartilaginous tissue located between the condyle of the mandible and glenoid fossa and articular eminence of the temporal bone. Damage or derangement of the TMJ disc can require surgical removal (discectomy) to restore function. Removal of the TMJ disc, however, leaves the joint space vulnerable to condylar remodeling and degradation, potentially leading to long-term complications. No consistently effective clinical option exists for repair or replacement of the disc following discectomy. This study investigates the use of an acellular scaffold composed of extracellular matrix (ECM) derived from small intestinal submucosa (SIS) as a regenerative template for the TMJ disc in a porcine model. Acellular SIS ECM scaffolds were implanted following discectomy and allowed to remodel for 2, 4, 12, and 24 weeks postimplantation. Remodeling of the implanted device was assessed by longitudinal magnetic resonance imaging (MRI) over the course of 6 months, as well as gross morphologic, histologic, biochemical, and biomechanical analysis (tension and compression) of explanted tissues (disc and condyle) at the time of sacrifice. When the scaffold remained in the joint space, longitudinal MRI demonstrated that the scaffolds promoted new tissue formation within the joint space throughout the study period. The scaffolds were rapidly populated with host-derived cells and remodeled with formation of new, dense, aligned fibrocartilage resembling native tissue as early as 1 month postimplantation. De-novo formation of peripheral muscular and tendinous attachments resembling those in native tissue was also observed. The remodeled scaffolds approached native disc biochemical composition and compressive modulus, and possessed 50% of the tensile modulus within 3 months postimplantation. No degradation of the condylar surface was observed. These results suggest that this acellular bioscaffold fills a medical need for which there is currently no effective treatment and may represent a clinically relevant "off-the-shelf" implant for reconstruction of the TMJ disc.

Project description:Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl expression, in which JNK and/or Ca(2+)/NFAT pathways were involved and therefore were engaged in enhancing the migration and differentiation of osteoclast precursors, leading to increased osteoclast activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated rats.

Dataset Information

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

Publications

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

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