Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus.

We examined the expression of galectin-1, an endogenous lectin with one carbohydrate-binding domain, in the adult mouse hippocampus after systemic kainate administration. We found that the expression of galectin-1 was remarkably increased in activated astrocytes of the CA3 subregion and dentate gyrus of the hippocampus, and in nestin-positive neural progenitors in the dentate gyrus. Quantitative reverse transcription PCR (RT-PCR) analysis revealed that the galectin-1 mRNA level in hippocampus began to increase 1 day after kainate administration and that a 13-fold increase was attained within 3 days. Western blotting analysis confirmed that the level of galectin-1 protein increased to more than three-fold a week after the exposure. We showed that isolated astrocytes express and secrete galectin-1. To clarify the significance of the increased expression of galectin-1 in hippocampus, we compared the levels of hippocampal cell proliferation in galectin-1 knockout and wild-type mice after saline or kainate administration. The number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells detected in the subgranular zone (SGZ) of galectin-1 knockout mice decreased to 62% with saline, and to 52% with kainate, as compared with the number seen in the wild-type mice. Most of the BrdU-positive cells in SGZ expressed doublecortin and neuron-specific nuclear protein, indicating that they are immature neurons. We therefore concluded that galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the hippocampus.

MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinson's disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MTH1-null mice exhibited a greater accumulation of 8-oxoG in mitochondrial DNA accompanied by a more significant decrease in TH and dopamine transporter immunoreactivities in the striatum after MPTP administration, than in wild-type mice. We thus demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

Pathologic gene expression in adhesive subacromial bursae of human shoulder.

An adhesion of the subacromial bursa in the shoulder causes pain during joint motion and restricts the range of motion of the glenohumeral joint. To understand the biologic features of an adhesion, the gene expressions in adhesive subacromial bursa were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. The gene expressions in adhesive subacromial bursae were approximately threefold to fourfold greater than those in nonadhesive bursae for the genes for Type I and Type III procollagens, CD34 antigen in vascular endothelium, hyaluronan synthase-3, and interferon-gamma. The gene expression of interleukin-8 was predominant in adhesive bursa. The gene expressions of hyaluronan synthase-1, hyaluronan synthase-2, and interleukin-10 which is an antiadhesive cytokine were predominant in nonadhesive bursae. Chromatography analysis revealed that a hyaluronan, of which molecular weight was more than 100 kDa, was present in the cavity of nonadhesive subacromial bursae. It is suggested that pathologic fibrosis and vascularization are maintained by the presence of interferon-gamma and interleukin-8 in adhesive subacromial bursae and that high molecular weight hyaluronan or interleukin-10 plays a role for antiadhesion.

Alteration of collagen network and negative charge of articular cartilage surface in the early stage of experimental osteoarthritis.

Forty-eight mature male Japanese white rabbits were subjected to unilateral resection of a segment of the gluteal muscles at the sacral origin and a section of infrapatellar ligament. Animals were killed at 1, 2, 4, and 8 weeks postoperatively, and the articular cartilage of the femoral heads was evaluated. The collagen fibrillar network of the articular surface was observed by scanning electron microscopy (SEM) using microdissection by ultrasonication. Cationized ferritin (CF) was used for the labeling of negative charges on the articular surfaces and the thickness of CF layers was observed under the transmission electron microscope. Metachromasia of the matrix decreased remarkably at 4 weeks postoperatively, and fibrillation of the articular surface was evident at 8 weeks postoperatively. Derangement and rupture of the collagen network developed as early as 1 week after surgery. The thickness of the CF layer significantly decreased at 4 weeks postoperatively. This study confirms that alterations of the articular surface, such as derangement of the collagen network and loss of the negative charge, are some of the earliest changes in osteoarthritis. In addition, application of ultrasonication with proper frequencies to the articular cartilage effects an optimal removal of mucus, with the consequent exposure of a well-preserved articular surface for SEM study.

Evaluation of core decompression for early osteonecrosis of the femoral head.

Twenty-six hips (19 patients) with osteonecrosis of the femoral head with stage I or II of the disease, according to the Ficat and Arlet classification, underwent core decompression. Osteonecrosis was confirmed histologically in all 26 hips. Of 19 patients, 7 had prognostic factors traditionally associated with poor outcome including collagen vascular disease and continued use of steroids. The follow-up period averaged 7 years 10 months (range: 2 years 5 months-13 years 8 months) for 17 patients with 24 hips. Two patients died secondary to systemic illness. Seventeen hips (65.4%) had very good or good results using the Ficat criteria. Eight hips (30.8%) needed further operation [total hip arthroplasty (THA) for 7 hips, osteotomy for 1 hip]. Of the 12 hips in patients who had used steroids, 6 hips (50%) were converted to THA. Four hips in patients with systemic lupus erythematosus (SLE) needed THA (100%). We conclude that core decompression provides an effective treatment for steroid-associated osteonecrosis other than in cases with SLE, as well as providing effective treatment for non-steroid-associated osteonecrosis in the early stages of the disease.