Increased expression of transthyretin in leptin-deficient ob/ob mice is not causative for their major phenotypic abnormalities.

The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass. By genome-wide expression analysis using hypothalamus RNA from wild-type and ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction. Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels. Although all of these parameters were identical to wild-type controls in Ttr-deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly, all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age. Taken together, our data demonstrate that the increased expression of Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.

Identification of molecular markers for articular cartilage.

OBJECTIVE: The aim of the current study was to identify molecular markers for articular cartilage (AC) that can be used as tools for the quality control of tissue engineered (TE) cartilage. DESIGN: A genome-wide expression analysis was performed using RNA isolated from articular and growth plate (GP) cartilage, both extracted from the knee joints of 6 weeks old minipigs. After confirming the specific expression for selected genes by RT-PCR, these were used as molecular markers for the quality control of TE cartilage. RESULTS: Albeit several known chondrocyte markers were expressed to a similar extent in articular and GP cartilage, our genome-wide expression analysis led us to identify genes being selectively expressed in either GP or articular chondrocytes. These findings led us to perform a RT-PCR expression analysis for the corresponding genes to demonstrate the absence of GP-specific markers in TE cartilage, while common or AC markers were expressed. CONCLUSIONS: Taken together, these results provide important novel insights into chondrocyte biology in general and AC in particular. In addition, it is reasonable to speculate, that some of the identified genes play distinct roles in the regulation of articular chondrocyte differentiation and/or function, thereby raising the possibility that they may serve as targets for non-operative therapies of osteoarthritis (OA).

Gap junctional communication in human osteoclasts in vitro and in vivo.

Bone-forming cells are known to be coupled by gap junctions, formed primarily by connexin43 (Cx43). The role of Cx43 in osteoclasts has so far only been studied in rodents, where Cx43 is important for fusion of mononuclear precursors to osteoclasts. Given the potential importance for human diseases with pathologically altered osteoclasts, we asked whether a similar influence of Cx43 can also be observed in osteoclasts of human origin. For this purpose, Cx43 mRNA expression was studied in a time course experiment of human osteoclast differentiation by RT-PCR. Localization of Cx43 in these cells was determined by immunohistochemistry and confocal microscopy. For the assessment of the effect of gap junction inhibition on cell fusion, gap junctions were blocked with heptanol during differentiation of the cells and the cells were then evaluated for multinuclearity. Paraffin sections of healthy bone and bone from patients with Paget's disease and giant cell tumour of the bone were used to study Cx43 expression in vivo. We found mRNA and protein expression of Cx43 in fully differentiated osteoclasts as well as in precursor cells. This expression decreased in the course of differentiation. Consistently, we found a lower expression of Cx43 in osteoclasts than in bone marrow precursor cells in the histology of healthy human bone. Blockade of gap junctional communication by heptanol led to a dose-dependent decrease in multinuclearity, suggesting that gap junctional communication precedes cell fusion of human osteoclasts. Indeed, we found a particularly strong expression of Cx43 in the giant osteoclasts of patients with Paget's disease and giant cell tumour of the bone. These results show that gap junctional communication is important for fusion of human mononuclear precursor cells to osteoclasts and that gap junctional Cx43 might play a role in the regulation of size and multinuclearity of human osteoclasts in vivo.

The relation between well-being, impostor feelings, and gender role orientation among Canadian university students.

A theoretical model of well-being identifies 6 key components that have been examined primarily in older adults (e.g., C. D. Ryff, 1989c, 1991): self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth (C. D. Ryff, 1995; C. D. Ryff & C. L. M. Keyes, 1995; C. D. Ryff & B. Singer, 1996). The authors examined them in a sample of 379 Canadian university students to determine how well-being was correlated with endorsement of stereotypic gender roles and with the impostor phenomenon. The participants completed Ryff's Scales of Psychological Well-Being (Ryff, personal communication, March 1996), the Clance Impostor Phenomenon Scale (P. R. Clance & M. A. O'Toole, 1988), and the Extended Personal Attributes Questionnaire (J. T. Spence, R. L. Helmreich, & C. K. Holahan, 1979). The results supported the hypotheses that (a) people with higher scores for expressive traits score higher for well-being stemming from positive relations with others, (b) people with higher scores for instrumental traits score higher for well-being related to feelings of autonomy, (c) people with higher scores for impostor feelings (and lower scores for ability confidence) score lower for self-acceptance and (d) for environmental mastery.