Robert S.B. Liem

Osteoarthritis and internal derangemen of the temporomandibular joint: A light microscopic study

To describe osteoarthritic changes of the temporomandibular joint (TMJ) and their relation to internal derangements, 22 randomly selected TMJ autopsy specimens were dissected and studied by light microscopy. Normal disc position was seen in eight joints, partial anterior displacement of the discs in eight joints, and complete anterior displacement of the discs in five joints; one joint had a perforated disc. Degenerative changes, such as horizontal splitting, clustering of chondrocytes, bone marrow fibrosis, sclerosis, erosion, cyst formation, and reduction in TMJ size, were found in 11 of the 14 joints with displacement or perforation of the disc and in four of the eight joints with normal disc position. Internal derangement appeared to be associated with osteoarthritis. The relations between remodeling, aging, internal derangement, and osteoarthritis are discussed.

The structure, biochemistry, and metabolism of osteoarthritic cartilage: A review of the literature

PURPOSE To understand the possible significance of the presence of proteases, cytokines, growth factors, and arachidonic acid metabolites in the osteoarthritic temporomandibular joint (TMJ), the pathogenesis of TMJ osteoarthritis (OA) is discussed, based on knowledge of structure, biochemistry and metabolism of osteoarthritic cartilage in general, and a classification of TMJ OA is presented.

Vesicle-Mediated Transport and Release of CCL21 in Endangered Neurons: A Possible Explanation for Microglia Activation Remote from a Primary Lesion

Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.

Expression of interleukin-1 beta in rat dorsal root ganglia

The expression of interleukin-1beta was examined in dorsal root ganglion (DRG) neurons from adult rats using non-radioactive in situ hybridization and immunocytochemistry. At all spinal levels, approximately 70% of the DRG neurons appeared to express IL-1beta mRNA; about 80% of these DRG neurons actually appeared to produce the IL-1beta protein at markedly varying levels. The expression of IL-1beta was found in large as well as in intermediate diameter sensory neurons but only sporadically in the population of small sensory neurons. The population of IL-1beta immunopositive sensory neurons included most of the large calretinin-positive Ia afferents, but only a few of the small substance P/CGRP positive sensory neurons. In situ hybridization staining for the detection of type 1 IL-1 receptor showed expression of this receptor by most of the sensory neurons as well as by supportive glial-like cells, presumably satellite cells. The functional significance of IL-1beta in the DRG neurons needs to be elucidated, but we speculate that IL-1beta produced by DRG neurons may be an auto/paracrine signalling molecule in sensory transmission.

Olig2 overexpression induces the in vitro differentiation of neural stem cells into mature oligodendrocytes

Differentiation induction of neural stem cells (NSCs) into oligodendrocytes during embryogenesis is the result of a complex interaction between local induction factors and intracellular transcription factors. At the early stage of differentiation, in particular, the helix‐loop‐helix transcription factors Olig1 and Olig2 have been shown to be essential for oligodendrocyte lineage determination. In view of the possible application of NSCs as a source for remyelinating cell transplants in demyelinating diseases (e.g., multiple sclerosis), in vitro procedures need to be developed to drive the oligodendrocyte differentiation process. Mere culture in medium supplemented with major embryonic oligodendrogenic induction factors, such as Sonic hedgehog, results in oligodendrocyte differentiation of only about 10% of NSCs. We previously showed that induction of Olig1 expression by gene transfection could indeed initiate the first stage of oligodendrocyte differentiation in NSCs, but appeared to be unable to generate fully mature, functional oligodendrocytes. In this study, we transfected NSCs isolated from the embryonic mouse brain with the Olig2 gene and found that the introduced overexpression of Olig2 could induce the development of fully mature oligodendrocytes expressing the transcription factor Nkx2.2 and all major myelin‐specific proteins. Moreover, Olig2‐transfected NSCs, in contrast to nontransfected NSCs, developed into actively remyelinating oligodendrocytes after transplantation into the corpus callo‐sum of long‐term cuprizonefed mice, an animal model for demyelination. Our results show that transfection of genes encoding for oligodendrogenic transcription factors can be an efficient way to induce the differentiation of NSCs into functional oligodendrocytes.

NORMAL CARTILAGE STRUCTURE, BIOCHEMISTRY, AND METABOLISM - A REVIEW OF THE LITERATURE

PURPOSE To understand the possible significance of the presence of proteases, cytokines, growth factors, and arachidonic acid metabolites in the osteoarthritic temporomandibular joint (TMJ), a review of the normal physiologic processes and participating factors in the normal TMJ is established, based on knowledge of structure, biochemistry and metabolism of normal cartilage in general.

Osteoarthritis of the temporomandibular joint: A light microscopic and scanning electron microscopic study of the articular cartilage of the mandibular condyle

The aim of this study was to investigate the organization of collagen fibrils and the histopathologic alterations as well as the morphologic aspects of osteoarthritic articular cartilage of the human mandibular condyle. Nine osteoarthritic condyles, three obtained at necropsy and the other six during surgery, were examined by light microscopy and scanning electron microscopy. Light microscopic observations revealed features of progressive and regressive remodeling and the presence of clefts. Scanning electron microscopic observations showed the presence of thick, coiled fibrils at the joint surface and numerous osmiophilic lipid globules scattered between the collagen fibrils. The collagen fibrils were disordered. It was concluded that collagen fiber network disintegration and fatty degeneration comprise the osteoarthritic changes of the articular cartilage of the human mandibular condyle.

Synovial inflammation in arthroscopically obtained biopsy specimens from the temporomandibular joint : A review of the literature and a proposed histologic grading system

Data indicate that the synovial lining of the temporomandibular joint (TMJ) in some respects differs from other joints. The normal variation in morphology of the synovial lining of the TMJ is quite great, whereas the variation in pattern of pathologic changes appears to be relatively small (ie, synovial inflammation is not of the severity as that in other joints). In the current review, a system for histologic grading of synovial inflammation is proposed. The system is based on semiquantitative evaluation of the following set of parameters: 1) synovial lining cell layers; 2) vascularity (number or size of vascular profiles); and 3) Inflammatory cell infiltrate (commonly lymphocytes).

Ultrastructure of the articular cartilage of the mandibular condyle aging and degeneration

To obtain more insight into the pathogenesis of osteoarthrosis of the temporomandibular joint, we examined the ultrastructure of articular cartilage of six healthy and sixteen osteoarthrotic human mandibular condyles. Ultrastructural changes due to aging and osteoarthrosis are described and compared with the findings of other ultrastructural studies of articular cartilage of synovial joints. Aging was accompanied by some slight degenerative signs. Osteoarthrotic hyaline cartilage and fibrocartilage showed a striking similarity. The only ultrastructural difference was the presence of elastic fibers in the latter. Therefore, both seem to have the same pathogenesis. Several current statements on the pathogenesis of osteoarthrosis are discussed.

Synovial membrane involvement in osteoarthritic temporomandibular joints : A light microscopic study

OBJECTIVE To study the light microscopic characteristics of the synovial membrane of osteoarthritic temporomandibular joints to evaluate synovial membrane involvement in the osteoarthritic process. STUDY DESIGN Synovial membrane biopsies were obtained during unilateral arthroscopy in 40 patients. Thirty-one temporomandibular joints were diagnosed with osteoarthritis. Osteoarthritis subgroups were defined on the basis of the presence of symptoms related to disk displacement and perforation. The control group consisted of nine temporomandibular joints that were not involved by osteoarthritis. During light microscopic examination of the synovial membranes, several light microscopic variables were recorded. Differences between groups and between subgroups were tested with chi 2 or Fishers exact tests with Mann-Whitney U tests and with Students t tests. RESULTS In the osteoarthritis group, the number of synovial intima cell layers was significantly higher, and fibrous intima matrix and fibrous subintima were found significantly more frequently than in the control group. Moreover, in the osteoarthritis group, intima cell hypertrophy in combination with a closely packed cell composition was found significantly more often in the first year of clinical signs and symptoms, whereas intima hyperplasia, fibrous intima matrix, dense surface material, and subintima elastic fibers were found significantly more frequently in the first 2 years of clinical signs and symptoms. CONCLUSIONS The findings in this study suggest that osteoarthritis of the temporomandibular joint may initially result in synovial intima hyperplasia and cell hypertrophy, and subsequently in deposition of fibrous material in the intima matrix. Eventually, fibrosis of the subintimal tissue may occur in combination with degeneration and subsequent normalization of the synovial intima cell layer. Overall, fibrosis was the most characteristic feature of synovial membranes of osteoarthritic temporomandibular joints. In conclusion, the involvement of the synovial membrane in osteoarthritis of the temporomandibular joint is characterized by an early proliferative phase and a late fibrous phase. It appears that the intense and prolonged fibrous phase may not be a normal appropriate response to an initial insult but rather an aberrant counterproductive response.