Objective: It is known that bone mineral density (BMD) and the strength of bone is predicted by body mass. Fat mass is a significant predictor of bone mineral density which correlates with body weight. This suggests that body fat regulates bone metabolism first by means of hormonal factors and second that the effects of muscle and loading are signaling factors in mechanotransduction. Leptin, a peptide hormone produced predominantly by white fat cells, is one of these hormonal factors. The aim of this study was to investigate and measure by micro-CT the different effects of weight-bearing on trabecular bone formation in mice without the stimulation of leptin. Results: Animals with an ad-libitum-diet (Group A) were found to increase body weight significantly at the age of six weeks in comparison with lean mice (Group B). From this point on, the difference increased constantly. At the age of twenty weeks the obese mice were almost twice as heavy as the lean mice. Significant statistical differences are shown between the two groups for body weight and bone mineral density. Examination of trabecular bone (BV/TV, trabecular number (Tb.N.), trabecular thickness (Tb.Th.)) revealed that the only statistically significant difference between the two groups was the Tb.N. for the proximal femur. High weight-bearing insignificantly improved all trabecular bone parameters in the obese mice. Compared with the control-diet Group B, the BV/TV and Tb.N. were slightly higher in the controlled-diet Group A, but not the Tb.Th.. However, correlation was found between Tb.N. and BMD on the one hand and body weight on the other hand. Conclusion: biomechanical loading led to decreased bone mineral density by a decrease in the number of trabeculae. Trabecular thickness was not increased by biomechanical loading in growing mice. Decreased body weight in leptin-deficient mice protects against bone loss. This finding is consistent with the principle of light-weight construction of bone. Differences in cortical and trabecular bone will be examined in later studies. It is not possible to conclude that these results also apply to human beings.
Objective: Mechanotransduction is the mechanism that due to reacting chondrocytes on biomechanical loading of body mass. Higher biomechanical loading lead to increased degeneration of chondrocytes, whereas moderate loading is protecting. This suggests that body fat regulates bone metabolism first by means of hormonal factors and second that the effects of muscle and loading are signaling factors in mechanotransduction. Leptin, a peptide hormone produced predominantly by white fat cells, is one of these hormonal factors. The aim of this study was to investigate and measure the different effects of weight-bearing on trabecular bone formation in mice without the stimulation of leptin and with or without osteoarthritis. Materials and methods: 40 C57BL/ 6J ob/ob-mice in the age of 20 weeks have been devided into two groups with an ad-libitum-diet and with reduced diet. The hip-and knee-joints have been examinated in micro-CT-scan and histomorphologically. Results: Animals with an ad-libitum-diet were found to increase body weight significantly at the age of six weeks in comparison with lean mice. At the age of twenty weeks the obese mice were almost twice as heavy as the lean mice. Significant statistical differences are shown between the two groups for body weight and bone mineral density. Examination of trabecular bone in micro-CT revealed that the only statistically significant difference between the two groups was the trabecular number for the proximal femur. High weight-bearing insignificantly improved all trabecular bone parameters in the obese mice. Correlation was found between trabecular number and bone mineral density on the one hand and body weight on the other hand. The correlation between body weight and osteoarthritis shows a significant increase in grade of osteoarthritis as body weight increases in hip-joint and knee-joint but not in osteoarthritis-positive (OP) versus osteoarthritis-negative (ON) mices. The correlation of the hip-joint between micro-CT data and body weight shows an increase in these data as body weight increases in OP mices. The correlation of the hip-joint between micro-CT data and osteoarthritis shows a decrease in these data as osteoarthritis increases in OP mices. The correlation of the knee-joint between micro-CT data and body weight shows differencies between ON and OP mices. The correlation of the knee-joint between micro-CT data and osteoarthritis shows an increase in these data as osteoarthritis increases in OP mices. Conclusion: biomechanical loading led to decreased bone mineral density by a decrease in the number of trabeculae. Trabecular thickness was not increased by biomechanical loading in growing mice. Decreased body weight in leptin-deficient mice protects against bone loss. This finding is consistent with the principle of light-weight construction of bone. Differences in osteoarthritis-positive and osteoarthritis-negative mices show the eventual importance of diet in leptin-deficience. It is not possible to conclude that these results also apply to human be...
Leptin is a peptide hormone produced predominantly by white fat cells [1,47]. The mature protein, encoded by the obesity (ob) gene localized in human and mouse 7 and 6 chromosomes, respectively, is a 16 kDa non-glycosylated protein. Leptin levels in the blood are proportional to adipose tissue mass. Initially discovered as a central regulator of appetite and energy expenditure, leptin levels can be considered as a signal to the body regarding its energy reserves. Although elevated leptin levels are present in obesity, it is likely that the physiological importance of leptin is that low levels indicate a state of starvation [2]. Recent data suggest that leptin may regulate a variety of other physiological processes, such as insulin action [7], hemopoiesis [5], immune function [28], reproduction [40], angiogenesis [26], and bone development and remodeling [19]. However, it is not clear whether leptin is a stimulator or an inhibitor of bone growth in humans. Some investigators noted a positive relationship between serum leptin levels and bone mineral density (BMD). Iwamoto et al. described a weakly correlation of serum leptin level with bone mineral density of pelvis and left leg in the premenopausal women and Odebasi et al. found that there was no correlation between plasma leptin concentrations and BMD values in healthy postmenopausal woman but a weak correlation was observed in postmenopausal woman with osteoporosis [23,35]. Whereas others observed a negative relationship. Blum et al. suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women [6]. Sato et al. suggest that an increase in serum leptin reduces bone formation and decreases BMD in adult men [42]. Furthermore, no associations between serum leptin levels and BMD have been reported, which further confounds the interpretation of leptin's effect on bone mass. Martini et al. conclude that serum leptin have no direct effect on bone mass and bone turnover in healthy postmenopausal women [32] and Rauch et al. appear that leptin has less influence on the mature than on the growing skeleton [41]. Only a few studies in humans have examined the direct effect of leptin administration on BMD. Ogueh et al. [36] Leptin was found to be involved in regulation of bone development and remodeling. This study was performed to evaluate the effects of biomechanical loading due to body weight in leptin-defient ob/ob mice at the same pubertal stage. No significant difference was found between the two groups for all the parameters (p>0.05) suggesting that the presence of leptin may be an important pre-condition for positive correlation between loading and bone mass. Furthermore, concordance of bone formation was found among appendicular regions, but was not found between the axial and appendicular regions.
ZusammenfassungDas in den Fettzellen produzierte Hormon Leptin reguliert die Reifung und Entwicklung des Knochens. Nicht bekannt ist jedoch dessen Einfluss auf das wachsende Skelett und die Gelenke. Unter Ausschluss der hormonellen Wirkung von Leptin wird die Auswirkung unterschiedlichen Körpergewichtes auf die Arthroseentstehung während der Wachstumsphase untersucht.Beginnend mit einem Alter von fünf Wochen wurden zwei Gruppen von je 20 weiblichen Leptin-defizienten ob/ob-Mäusen untersucht. Gruppe A erfuhr keine Einschränkung der Futtermenge, während Gruppe B einer kontrollierten Diät unterzogen wurde. Die Strukturen der Hüftund Knie-Gelenke wurden histomorphologisch mittels Hämatoxylin-Eosin-Färbung (HEFärbung) und Elastica-van-Gieson-Färbung (EVG) untersucht. Die Einteilung der Arthrose erfolgte nach dem Schema nach Otte von 1969. Es werden insgesamt vier Stadien unterschieden.Im Alter von 20 Wochen lag das Körpergewicht der Gruppe A signifikant höher als in der Gruppe B (p < 0,05) und es zeigt sich ein signifikanter Unterschied der beiden Gruppen im Arthrosegrad (p > 0,05).Leptin stellt einen wichtigen Faktor für eine positive Korrelation zwischen der Belastung und der Knochenmasse dar. Wird dies berücksichtigt, kommt es in Gruppe B zu einem höheren Arthrosegrad, so dass wir vermuten, dass bereits in der Knochen- und Gelenk reifung der Einfluss von Leptin von entscheidender Bedeutung ist, und dass übermäßiges Übergewicht im Jugendalter mit relativer Leptininsuffizienz zu vorzeitigem Gelenkverschleiß führt.
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