TMJ disorders: future innovations in diagnostics and therapeutics

Abstract

Because their etiologies and pathogenesis are poorly understood, temporomandibular joint (TMJ) diseases are difficult to diagnose and manage. All current approaches to treatments of TMJ diseases are largely palliative. Definitive and rational diagnoses or treatments can only be achieved through a comprehensive understanding of the etiologies, predisposing factors, and pathogenesis of TMJ diseases. While much work remains to be done in this field, novel findings in biomedicine and developments in imaging and computer technologies are beginning to provide us with a vision of future innovations in the diagnostics and therapeutics of TMJ disorders. These advances include the identification and use of local or systemic biomarkers to diagnose disease or monitor improvements in therapy; the use of imaging technologies for earlier and more sensitive diagnostics; and the use of biomedicine, biomimetics, and imaging to design and manufacture bioengineered joints. Such advances are likely to help to customize and enhance the quality of care we provide to patients with TMJ disorders.

Figure 1. Gross anatomy, organization, and histology of the TMJ

A. Skeletal components that make up the TMJ include the glenoid fossa (GF) and articular eminence (AE) of the temporal bone (TB), the mandibular condyle (MC), and the intervening articular disc (AD), which are surrounded by the synovial capsule (SC). B. Histology of the mandibular condylar cartilage demonstrates four distinct zones: a-articular, b-polymorphic or proliferative, c-flattened or chondroblastic, and d-hypertrophic.

Figure 2. Relaxin with or without estrogen decreases the proteoglycan content of TMJ disc fibrocartilage

TMJ discs cultured in control medium (Ct) or in the presence of relaxin (R) or estrogen plus relaxin (E+R) were stained for proteoglycans (stained red), a major matrix molecule in the disc. Discs cultured with relaxin or estrogen plus relaxin showed approximately 50 percent reduction in proteoglycan content. Data from: Naqvi T, Duong TT, Hashem G, Shiga M, Zhang Q, Kapila S. Relaxin’s induction of metalloproteinases is associated with the loss of collagen and glycosaminoglycans in synovial joint fibrocartilaginous explants. Arthritis Res Ther 2005;7:R1–11.

Figure 3. Sections of the TMJ from nine-month-old wild type (WT) (A and C) and biglycan/fibromodulin double knockout (DKO) mice (B and D) stained with hematoxylin and eosin

The arrowheads show vertical clefts, the asterisks show the small acellular areas under the articular surfaces, and the arrow shows regions where chondrocytes lose their regular columnar organization and form clusters. Reprinted with permission from Wadhwa S, Embree MC, Kilts T, Young MF, Ameye LG. Accelerated osteoarthritis in the temporoman-dibular joint of biglycan/fibromodulin double-deficient mice. Osteoarthritis Cartilage 2005;13:817–27.

Figure 4. New opportunities for additional diagnostic information available with conebeam CT systems

Conebeam computed tomographic images can be manipulated to derive three-dimensional volumetric images that can be viewed from any perspective with superimposing tissues dissected out to clearly visualize the region of interest (A to D) or sections of desired thicknesses derived in any plane of interest—in this case, axial (E), coronal (F), and sagittal (G) views of the TMJ.

Figure 5. A macromolecular contrast agent, albumin-(Gd-DTPA)30 in conjunction with dynamic MRIs provides quantitative and sensitive data on the magnitude of vascular permeability and extravasation that correlates very highly with the severity of joint inflammation

The upper panel demonstrates precontrast (A) and 30-minute postcontrast (B) coronal section of MR images from a control rabbit with no joint inflammation. The postcontrast image shows the expected enhancement of blood vessels (BV), the cavernous sinus (CS), and other vascular structures, but only minimal enhancement in the synovium of the TMJs (arrowheads). On the other hand, rabbits with TMJ inflammation showed a gradual increase in enhancement of the inflamed synovium from the precontrast time point (C) to 2 (D), 10 (E), and 30 (F) minutes after intravenous administration of the contrast agent (depicted by arrows and arrowheads). The histologic total arthritic score was highly correlated to the rate of tissue enhancement. R=rami of mandible; B=brain; C=condylar heads; M=masseter muscle; R=right. Reprinted with permission from van Dijke CF, Kirk BA, Peterfy CG, Genant HK, Brasch RC, Kapila S. Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings. Radiology 1997;204:825–32.

Figure 6. Mesenchymal stem cells can be stimulated to undergo differentiation into different cell lineages, including muscle, bone, cartilage, and ligament, which can be used to derive the entire TMJ complex

Commitment to a particular lineage is driven by the presence of local morphogenic factors. Lineage-committed cells progress through a number of transitory stages. Once differentiation is initiated, proliferation is down regulated, and tissue-specific proteins are expressed to generate the specific tissue. It is thought that mesenchymal stem cells are present in all organs of the body, where they serve to maintain tissue homeostasis. Reprinted with permission from Risbud MV, Shapiro IM. Stem cells in craniofacial and dental tissue engineering. Orthod Craniofac Res 2005;8:54–9.

Figure 7. Image-based design enables the construction of scaffolds that are defect site-specific

The image of the patient or animal condyle (A) is used to generate a computer microarchitecture structure of the desired implant design (B), which is used in turn to construct a solid free-form fabrication of the desired material or materials (C). Subsequently, the scaffold is seeded with cells and stimulated appropriately to generate bone and cartilage. Reprinted with permission from Schek RM, Taboas JM, Hollister SJ, Krebsbach PH. Tissue engineering osteochondral implants for temporomandibular joint repair. Orthod Craniofac Res 2005;8:313–9.

Figure 8. Composite scaffolds, shaped as the TMJ condyle, seeded with cells, and appropriately stimulated, generate osteochondral tissues mimicking the shape of the condyle

(A) Safranin-O and fast green staining shows pink-stained cartilage (arrows) in the condylar head in contact with the green-brown stained bone. (B) Hematoxylin and esoin staining of the hyaluronic acid portion of the scaffold shows the formation of bone (arrows) with marrow space. Reprinted with permission from Schek RM, Taboas JM, Hollister SJ, Krebsbach PH. Tissue engineering osteochondral implants for tem-poromandibular joint repair. Orthod Craniofac Res 2005;8:313–9.