Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats.

Although the MHC class II 'u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II 'a' and 'u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II 'a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis.

A longitudinal study for femoral neck bone mineral density increases in premenopausal caddies using dual-energy X-ray absorptiometry.

This longitudinal study examined whether bone mineral density (BMD) of the lumbar spine and proximal femur is maintained in premenopausal caddies (n = 6; mean age 37.8 years) in comparison with desk workers (n = 6; mean age 40.8 years) at the same golf club. BMD was followed for 12 months using dual-energy X-ray absorptiometry (DXA) and bone metabolic markers and athletic ability were also examined. Longitudinally, for caddies, the change per year in BMD of the lumbar spine was +0.009 g/cm2, while that of the proximal femur was +0.022 g/cm2, showing significant differences (P < 0.05 by signed-rank test). Their athletic ability, in terms of leg-press power, also significantly increased, whereas bone metabolic markers, such as serum alkaline phosphatase, 1,25-(OH), vitamin D3, parathyroid hormone and the deoxypyridiniline/creatinine ratio, did not show significant changes. For desk workers, the change per year in BMD of the lumbar spine was +0.011 g/cm2, while that of the proximal femur was -0.006 g/cm2. Their BMD, athletic ability and bone metabolic markers did not show significant changes. These findings support the results of our previous study, that premenopausal women can achieve continuous gain in femoral neck BMD by regular intense athletic activity, and suggest that this is also true by the continuous extensive walking of golf caddies.

Effects of hyaluronan on the healing of rabbit meniscus injured in the peripheral region.

The effect of hyaluronan (hyaluronic acid; HA) on the healing of rabbit meniscus injured in the peripheral region was assessed. A longitudinal tear was created in the peripheral region of the medial meniscus in 20 mature New Zealand white rabbits. One week after surgery, HA was injected into the left knee joint once a week for 5 weeks (HA group), while saline was injected into the right knee (control group). Six and 12 weeks after surgery, gross morphology, histology, and biochemical evaluations were performed. On gross morphological examination, there was evidence of meniscal healing in both groups, but the healing rate of the HA group was significantly higher than that of the control group at 12 weeks. Histologically, meniscal healing started at the tibial portion of the meniscal injury at 6 weeks in both groups, then advanced in the direction of the femoral surface at 12 weeks in the HA group. Biochemically, water and glycosaminoglycan contents did not differ significantly between the two groups. Hyaluronan maintained the healing process of the injured menisci, especially in the femoral surface, up to 12 weeks after injury.

Effects of hyaluronan on periosteal grafts for large full-thickness defects in rabbit articular cartilage.

We studied the effects of hyaluronan (HA) on chondrogenesis in periosteal grafts in rabbit knees to elucidate the effects of this agent in the repair of articular cartilage. Large full-thickness defects of the articular cartilage were created in the anteromedial part of the femoral articular surface of bilateral knee joints. Periosteal grafts were then harvested and sutured onto the defects. HA was injected in the right knee immediately after the operation and then once a week for 4 weeks (HA group). The same volume of saline was injected in the left knee in the control group. The animals were killed 2, 5, 8, and 12 weeks after the operation. Macroscopic and histological findings of the regenerated tissue were evaluated with a semiquantitative histological grading system. The total histological scores of the HA group were better than those in the control group at each time examination point. At 12 weeks, in particular, the scores for surface regularity and integration to adjacent articular cartilage were significantly better in the HA group than in the control group (P < 0.05). No significant differences were observed between the two groups in regard to the area healed (%). HA may have beneficial effects on the repair of large full-thickness defects of the articular cartilage with autologous periosteal grafts.