Angiopoietin-like protein 2 promotes chondrogenic differentiation during bone growth as a cartilage matrix factor.

OBJECTIVE: Chondrocyte differentiation is crucial for long bone growth. Many cartilage extracellular matrix (ECM) proteins reportedly contribute to chondrocyte differentiation, indicating that mechanisms underlying chondrocyte differentiation are likely more complex than previously appreciated. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor normally abundantly produced in mesenchymal lineage cells such as adipocytes and fibroblasts, but its loss contributes to the pathogenesis of lifestyle- or aging-related diseases. However, the function of ANGPTL2 in chondrocytes, which are also differentiated from mesenchymal stem cells, remains unclear. Here, we investigate whether ANGPTL2 is expressed in or functions in chondrocytes. METHODS: First, we evaluated Angptl2 expression during chondrocyte differentiation using chondrogenic ATDC5 cells and wild-type epiphyseal cartilage of newborn mice. We next assessed ANGPTL2 function in chondrogenic differentiation and associated signaling using Angptl2 knockdown ATDC5 cells and Angptl2 knockout mice. RESULTS: ANGPTL2 is expressed in chondrocytes, particularly those located in resting and proliferative zones, and accumulates in ECM surrounding chondrocytes. Interestingly, long bone growth was retarded in Angptl2 knockout mice from neonatal to adult stages via attenuation of chondrocyte differentiation. Both in vivo and in vitro experiments show that changes in ANGPTL2 expression can also alter p38 mitogen-activated protein kinase (MAPK) activity mediated by integrin α5ß1. CONCLUSION: ANGPTL2 contributes to chondrocyte differentiation and subsequent endochondral ossification through α5ß1 integrin and p38 MAPK signaling during bone growth. Our findings provide insight into molecular mechanisms governing communication between chondrocytes and surrounding ECM components in bone growth activities.

Control of an outbreak of highly pathogenic avian influenza, caused by the virus sub-type H5N1, in Japan in 2004.

An outbreak of highly pathogenic avian influenza (HPAI), caused by the virus sub-type H5N1, occurred at four premises in three prefectures in Japan during January and March 2004. As a result, 274,654 poultry died or were slaughtered. This was the first outbreak of HPAI in Japan since 1925. (The earlier outbreak was caused by H7N7.) The disease was successfully eradicated within three-and-a-half months, following an eradication campaign that included depopulating the affected premises, implementing movement controls and intensive surveillance. Control measures were conducted in accordance with the National Manual of HPAI Control. However, during the eradication campaign, some key issues arose, such as delays in notification by the affected farmers. As a result of these experiences, the relevant laws and HPAI Control Manual have been appropriately revised.

[Clinicopathological significance of immune complex (IC) along the tubular basement membrane (TBM) in lupus nephritis].

This paper reports on the clinicopathological significance of IC along the TBM in lupus nephritis. Renal biopsies were performed on 60 patients with SLE. All of the patients demonstrated immunoglobulin deposits in the glomeruli, and 16 of them also showed immune deposits along the TBM. The IgG in the glomeruli or along the TBM completely disappeared after incubation with human IgG, IgG Fc fragments, but not with human F(ab')2, rabbit or rat IgG. These results suggest that IgG along the TBM are similar in nature to IC in the glomeruli and that the IC are composed of IgG rheumatoid factor. The square of tubulointerstitial lesions was more severe in the group with IgG along the TBM than in the group with no IgG along the TBM (5.85 +/- 9.88% vs 1.29 +/- 3.72%). In addition of this, the group with IgG deposits along the TBM frequently demonstrated type IV lupus nephritis. Although the renal function was not significantly different in the both groups, the serum complement level was lower in the cases with IC deposits in the TBM. From these results, it is suggested that IC deposits along the TBM as one of the important inflammatory agents lead to the severe forms of tubulointerstitial injury and show the active stage of the disease in SLE patients.

Risk factors for the introduction of avian influenza virus into commercial layer chicken farms during the outbreaks caused by a low-pathogenic H5N2 virus in Japan in 2005.

Avian influenza outbreaks caused by a low-pathogenic H5N2 virus occurred in Japan from June to December 2005. All 41 affected farms housed layer chickens. Therefore, we conducted a case-control study targeting all commercial layer chicken farms within the movement restriction areas in Ibaraki prefecture, where most outbreaks were detected, to investigate the risk factors for the introduction of avian influenza virus (AIV). Four variables were identified as risk factors associated with the introduction of AIV by multivariate logistic regression: 'introduction of end-of-lay chickens ' (odds ratio (OR) = 36.6), 'sharing of farm equipment among farms' (OR = 29.4), 'incomplete hygiene measures of farm visitors on shoes, clothes and hands' (OR = 7.0), and 'direct distance to the nearest case farm' (0-500 m, OR = 8.6; 500-1000 m, OR = 0.8; 1000-1500 m, OR = 20.1; referenced more than 1500 m). We fully believe that strict biosecurity measures should be applied against any incursion points so as not to introduce AIV into more farms.