This study provides strong evidence that TNF-alpha is a key molecule in the control of the inflammatory changes that occur in the RA synovium. In addition, TNF-alpha regulates IL-6 production. However, other inflammatory pathways independent of TNF-alpha may contribute to the bone and cartilage damage seen in RA.
Objective. To elucidate the involvement of the regulatory CD4؉ T cells that produce high levels of interleukin-10 (IL-10) and low levels of IL-4 and IL-2 in the pathogenesis of rheumatoid arthritis (RA), we investigated whether the frequency of this type of CD4؉ T cell subset in peripheral blood lymphocytes (PBL) or synovial lymphocyte infiltrates of patients with RA correlated with disease severity and histologic features in rheumatoid synovium.
We have analyzed the radiologic findings on the lumbar spine and the clinical symptoms in patients with rheumatoid arthritis (RA). A total of 106 patients who fulfilled the revised criteria of the American Rheumatism Association were subjected. All of the patients were asked to fill out a questionnaire about the existence of low back pain, leg pain, and leg numbness. Radiologic features of the lumbar spine, including scoliosis, spondylolisthesis, disc space narrowing, endplate erosion, osteophyte, and osteoporosis, were checked. Radiographs of the cervical spine were also taken. The clinical background of RA, such as mutilating disease or not, was assessed. Forty-two patients (40%) had the symptoms of low back pain. Abnormal radiologic findings in lumbar spine were detected in 57%. The prevalence of clinical symptoms tended to be higher in the patients with endplate erosion. Forty-two percent of the patients had both lumbar and cervical lesions. The prevalence of lumbar lesion was not high in the mutilating type of RA, except for facet erosion and severe osteoporosis. The patients with pulse steroid therapy revealed a higher prevalence of vertebral fracture. From these results, we concluded that lumbar lesions were frequently observed in patients with RA. The possibility of lumbar lesions as well as the lesions in the cervical spine and peripheral joints should be examined in patients with RA.
The rate of bone formation is largely determined by the number of osteoblasts, which in turn is determined by the rate of replication of progenitors and the life span of mature cells, reflecting the timing of death by apoptosis. However, the exact age-dependent changes of the cellular activity, replicative potential, and life span of osteoblasts have not been investigated to date. Here, we present evidence that the cellular activity, telomere lengths, and replicative life span of osteoblastic cells obtained from juxta-articular bone marrow gradually decrease with the advance of donor age. Recently, telomerase reverse transcriptase (hTERT) has been identified as a human telomerase catalytic subunit. We transfected the gene encoding hTERT into telomerase-negative human osteoblastic cells from donors and osteoblastic cell strain NHOst 54881 cells and showed that expression of hTERT induces telomerase activity in these osteoblastic cells. In contrast to telomerase-negative control cells, which exhibited telomere shortening and senescence after 10 -15 population doublings, telomerase-expressing osteoblastic cells had elongated telomere lengths and showed continued alkaline phosphatase activity and procollagen I C-terminal propeptide (
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