Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy.

Renal osteodystrophy (ROD) is a major problem in patients with renal insufficiency. The present study was designed to elucidate the role of bone collagen changes and osteoblast differentiation in a rat model of ROD pathogenesis induced by adenine. Typical characteristics of renal failure, including increased serum urea nitrogen, creatinine, inorganic phosphorus, and intact parathyroid hormone levels, and decreased serum calcium and 1,25(OH)2D3 levels, were observed in adenine-induced rats. Micro-computed tomography analysis of the femur in adenine-induced rats showed decreased bone mineral density and osteoporotic changes, confirmed by the three-point bending test. The cancellous bone histomorphometric parameters of the tibia showed increased osteoblast number, decreased osteoclast surface with peritrabecular fibrosis, and increased osteoid tissue, indicating a severe mineralization disorder similar to clinical ROD. Scanning and transmission electron microscopy revealed irregular alignment and increased diameter of bone collagen fibrils in adenine-induced rats. Protein expression analysis showed greater accumulation of advanced glycation end products (AGEs) in peritrabecular osteoblasts of adenine-induced rats than in the controls. In contrast, suppressed expression of runt-related transcription factor 2, alkaline phosphatase, secreted phosphoprotein 1 (Spp1), and lysyl oxidase (Lox) mRNA levels, particularly the amount of active LOX protein, were observed. In in-vitro experiments, mineralizing MC3T3-E1 osteoblastic cells stimulated with AGE-modified bovine serum albumin had attenuated the expression of Spp1 mRNA levels and active LOX protein, with a decrease in extracellular nodules of mineralization. These observations provide clues to ROD pathogenesis, as they indicate that the suppression of osteoblast differentiation and decreased active LOX protein associated with accumulation of AGEs in osteoblasts caused structural abnormalities of bone collagen fibrils and a severe mineralization disorder, leading to bone fragility.

Inhibition of extracellular matrix integrity attenuates the early phase of aortic medial calcification in a rodent model.

BACKGROUND AND AIMS: The mechanism of vascular calcification (VC) resembles that of bone metabolism, and a correlation has frequently been reported between calcification and vascular extracellular matrix (ECM) regulating its integrity; however, the detailed mechanisms remain unclear. In this study, we examined how the vascular ECM, especially collagen metabolism, is involved in the process of VC. METHODS: VC was modeled using 5-week-old male Sprague-Dawley rats fed a diet containing warfarin and vitamin K1 (WVK). Additionally, ß-aminopropionitrile (BAPN) was administered to inhibit lysyl oxidase (LOX), which is an enzyme that mediates collagen cross-linking. Harvested aortic samples were analyzed by staining with alizarin red (AR), immunohistochemistry (IHC), transmission electron microscopy (TEM), and ex vivo microcomputed tomography (µCT). RESULTS: Rats fed WVK developed increasing numbers of aortic medial calcifications (AMCs) over time. TEM images indicated punctate calcification within collagen fibers in the early phase of AMC. AR staining of translucent samples revealed the distribution and severity of calcification, and these lesions were significantly decreased in the BAPN group. Three-dimensional reconstructed µCT images that allowed the quantification of calcified volumes revealed that BAPN significantly reduced the bulk of calcification. Moreover, IHC showed that both LOX and collagen I were present around the sites of AMC, and thus the IHC-positive area was reduced in the BAPN group compared to the WVK group. CONCLUSIONS: The results indicated that inhibition of LOX by BAPN attenuated AMC, and that collagen metabolism plays a significant role in the early pathogenesis of VC.

An Onchocerca species of wild boar found in the subcutaneous nodule of a resident of Oita, Japan.

Histological examination and dissection of a subcutaneous nodule removed from the right infraclavicular region of a 69-year-old woman from Oita, Kyushu, Japan, revealed a young female of Onchocerca dewittei japonica, a common parasite of wild boar in the Oita region. Distinctive morphologic characteristics of this Onchocerca species include the thick cuticle with very prominent and straight transverse ridges overlapping at the lateral sides, the lack of inner striae (scalloping) of the inner cuticle layer, the dorso-ventral symmetry, and the thick somatic muscles. Jointed with previous reports in the past decade, this case confirms the occasional transmission of the parasite from wild boar to humans in Oita.

Simulium (Gomphostilbia) taitungense, a new species of black fly (Diptera: Simuliidae) from Taiwan, with description of the male of Simulium (Gomphostilbia) tuenense Takaoka.

Simulium (Gomphostilbia) taitungense sp. nov. is described on the basis of reared adult, pupal and mature larval specimens collected from Taitung, Taiwan. This new species is placed in the ceylonicum species-group within the subgenus Gomphostilbia and is distinguished from related known species by the characteristic colour markings on the ventral surface of the head capsule and on the dorsal surface of the abdomen in the larva. The male of Simulium (Gomphostilbia) tuenense Takaoka, which was originally described from a pharate pupa and a larva, is described for the first time; the association of the adult stage with the larval stage was confirmed by the comparison of the sequences of the mitochondrial 16S rRNA gene; this species is also placed in the ceylonicum species-group.