The purpose of this study was to investigate the mechanism of cell death in chondrocytes of the growth plate. In the degenerative chondrocyte zone of the growth plate, apoptotic chondrocytes were defeated by the in situ nick end labelling method, by DNA analysis in agarose gel, and by electron microscopy. The results of the in situ nick end labelling method and the occurrence of a ladder pattern of DNA in agarose gel analysis indicated the activation of endogenous endonucleases, resulting in DNA fragmentation. Electron micrographs showed the early morphological changes associated with apoptosis. This report presents both morphological and biochemical evidence for apoptosis in the terminal hypertrophic chondrocytes of the growth plate. These data suggest that apoptosis of degenerative chondrocytes may play an important role in the control of normal and pathological endochondral ossification.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.

The histological grade of chondrosarcoma correlates well with their clinical behavior and with the patient's survival duration. We have previously demonstrated that p21 was expressed in the hypertrophic chondrocytes of the growth plate. To assess the relationship of p21 (waf1/cip1) to cell differentiation in chondrosarcoma, we examined the p21 expression in 14 cases of chondrosarcoma immunohistochemically and the induction of p21 by insulin-like growth factor-I (IGF-I) during cell differentiation in SW1353 chondrosarcoma cells. p21 immunoreactivity was seen in well-differentiated chondrosarcoma cells and was mutually exclusive with MIB1 reactivity in grade-1 chondrosarcoma. In vitro, the proteoglycan synthesis of SW1353 cells was increased by IGF-I in a dose-dependent manner. However, cell proliferation was not markedly stimulated. Overexpressions of p21 mRNA and p21 protein in SW1353 cells were induced by IGF-I 100 ng/ml. Our results suggested that the p21 expression was directly related to tumor differentiation and that the p21 expression was an important mediator for IGF-I in chondrosarcoma cells.

SUMMARYRDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-la and tumour necrosis factor-alpha (TNF-a)), interferon-gamma (IFN-y) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-la production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-a production was highest in the TCL from patients' PBMC. The levels of IFN-y or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-y, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-la in patients with RDC.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scienti€ic rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-l~ and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst iluid than in serum. Immunostaining of cells in the strorna and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1P in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-a, interleukin-6, and interleukin-lg. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.A solitary bone cyst is a fluid-filled cystic lesion that occurs in the metaphysis of long bones of children and adolescents. It is generally discovered because of a fracture due to an insignificant trauma or incidentally after a roentgenographic examination for other reasons (26). In recent times, traditional surgical treatment of the solitary bone cyst in the young has seldom been a first choice because of a high recurrence rate and the sacrifice of autogenous bone. A less invasive approach is the injection of methylprednisolone acetate into the cyst (25). Favorable results have been obtained with this method, although the pharmacologic mechanism by which this steroid promotes healing of the cyst is not yet clarified. A high bone-resorbing activity in the cyst fluid caused by prostaglandins, interleukin (TL)-l, and proteolytic enzymes has been reported (14). It also has been demonstrated that the cyst fluid has the oxygen free-radical activity (15). Steroids may have an inhibitory effect on bone resorption.Although the cause of the solitary bone cyst is unsettled, venous obstruction is believed to be an im-

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