ABSTRACT
OBJECTIVE: Trappins are small serine protease inhibitors bound to extracellular matrix (ECM) through the actions of transglutaminase (TGase) enzymes. Trappin-2 is present in many tissues and is upregulated at sites of injury. In osteoarthritis (OA), serine proteases contribute to articular cartilage destruction, and TGase activity is increased. Yet little is known about matrix-bound serine protease inhibitors or TGase substrates in articular cartilage. Our purpose was to determine if trappin-2 was present in OA cartilage and synovial fluid (SF). METHODS: OA knee articular cartilage and SF were assayed for trappin-2 protein by Western blotting, ELISA, and immunohistochemistry. Trappin-2 mRNA was detected with RT-PCR. The ECM components bound to trappin-2 were identified by 2-D gel electrophoresis and peptide fingerprinting. RESULTS: Trappin-2 was detectable in OA articular cartilage extracts, cultured chondrocytes, conditioned media, and SF by Western blotting. OA cartilage protein extracts contained significantly higher quantities of trappin-2 than normal cartilage protein extracts (22.98 +/- 1.28 ng/mg wet weight vs 14.97 +/- 1.92 ng/mg wet weight; p < 0.01). RT-PCR confirmed the presence of trappin-2 mRNA in OA chondrocytes. Immunohistochemical studies of OA cartilage revealed trappin-2 protein in chondrocytes. Peptide mapping of trappin-2 binding partners showed that fibromodulin was bound to trappin-2 in cartilage. CONCLUSION: We confirmed the presence of trappin-2 in OA cartilage and SF. Elevated levels of TGase activity in OA cartilage may increase levels of this serine protease inhibitor in response to injury.
Subject(s)
Cartilage, Articular/metabolism , Leukocyte Elastase/antagonists & inhibitors , Osteoarthritis/metabolism , Protein Precursors/metabolism , Synovial Fluid/metabolism , Adolescent , Adult , Cartilage, Articular/pathology , Cells, Cultured , Chondrocytes/metabolism , Chondrocytes/pathology , Culture Media, Conditioned/chemistry , Elafin , Humans , Immunoenzyme Techniques , Osteoarthritis/pathology , Protein Precursors/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Synovial Fluid/cytologyABSTRACT
OBJECTIVE: To review current literature on the gastrointestinal tract (GIT) manifestations of systemic sclerosis (SSc) and to report on 5 patients with severe gastrointestinal SSc. MATERIALS AND METHODS: The clinical course and histopathology of 5 patients are described. A review of the medical literature registered in MedLine and PreMedLine databases from 1996 through mid-2004 was performed using the keywords systemic sclerosis and scleroderma and combining them with text words such as gastric, gastrointestinal, anorectal, colonic, and hepatic. RESULTS: All 5 patients had severe GIT involvement: 4 with diffuse cutaneous SSc (dcSSc) and 1 with limited cutaneous SSc (lcSSc). Autopsy results of 2 patients who died from severe malnutrition and aspiration pneumonia are presented. Literature review includes involvement from oral cavity to anus with varying degrees of severity. Most GIT manifestations result from dysmotility secondary to infiltration of the gastrointestinal wall with fibrous tissue and can cause life-threatening malabsorption and malnutrition. Diagnostic tests, pathology, and treatments of GIT SSc are reviewed. CONCLUSIONS: GIT involvement in SSc can be severely debilitating and even life-threatening. Although morbidity is inevitable, appropriate supportive treatment can prolong survival. RELEVANCE: GI complications of SSc cause significant morbidity and mortality.
Subject(s)
Gastrointestinal Diseases/etiology , Scleroderma, Localized/complications , Scleroderma, Systemic/complications , Adult , Female , Gastrointestinal Diseases/mortality , Gastrointestinal Diseases/pathology , Humans , Middle AgedABSTRACT
Osteoarthritis is the most common form of arthritis in adults and its incidence increases with age. More than 50% of people aged 65 and older have radiographic changes of knee osteoarthritis. Calcium crystals, including calcium pyrophosphate dihydrate and basic calcium phosphate crystals, are also common in the elderly. Not surprisingly, osteoarthritis and crystal arthropathy frequently coexist. The question of a role for calcium crystals in causing or worsening osteoarthritis has been pondered for many years. Progress in understanding the interrelationships between calcium crystals and osteoarthritis has been slowed by our limited knowledge of the pathogenesis of both osteoarthritis and calcium crystal-induced arthritis and our limited ability to accurately detect calcium crystals. Nonetheless, there are good data from clinical and laboratory studies supporting an important role for calcium crystals in osteoarthritis.
