Cytokines In Bone Loss Research Articles

Alveolar bone loss in T helper 1/T helper 2 cytokine‐deficient mice

The role of cytokines in bone loss is important in the context of periodontitis, where inflammation-induced bone destruction is a major manifestation. Numerous cytokines have been implicated as mediators of bone resorption. The purpose of this study was to observe the impact of targeted gene deletion of T helper 1 (Th1) and T helper 2 (Th2) cytokines on naturally occurring alveolar bone loss in genetically modified mice. Alveolar bone loss was measured histomorphometrically in interleukin-4, interleukin-10, interleukin-12p40, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) knockout mice at 6, 16 and 30 wk of age. Both Th1 (interleukin-12p40, IFN-gamma, TNF) and Th2 (interleukin-10, interleukin-4) knockout mice exhibited significantly more alveolar bone loss than their respective wild-type control mice (p<0.001). Interleukin-10-/- and interleukin-12p40-/- mice exhibited a three-fold increase in alveolar bone loss at 30 wk of age, whereas bone loss in IFN-gamma-/-, TNF-/- and interleukin-4-/- mice was 1.5- to two-fold higher compared with wild-type control mice. The results of the present study indicate that both Th1 and Th2 cytokines play an important role in maintaining alveolar bone homeostasis. The kinetics of alveolar bone loss seen in cytokine gene knockout mice indicates that bone loss is age dependent and late in onset.

Increased bone resorbing activity of peripheral monocyte culture supernatants in elderly women.

Accelerated bone loss occurs in the years after menopause, and is an ongoing phenomenon in elderly women. The role of cytokines in bone loss after estrogen deficiency has been shown in ovariectomized rat and mice models. In humans, the involvement of bone resorbing cytokines is now well established. In the early years after menopause, monocyte activation leads to increased cytokine production. We have previously shown that the bone resorbing activity (BRA) of peripheral blood monocyte culture supernatants from postmenopausal women is higher than in premenopausal (Pre-M) women. This increased activity was related to interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha levels. We here investigate whether monocyte activation still occurs in older women and whether this relates to bone resorption. We studied 19 healthy Pre-M, and 24 early (E-Post-M, menopause < 10 yr) and 24 late (L-Post-M, menopause > 10 yr) postmenopausal women. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma. BRA of monocyte supernatants (expressed as the ratio of monocyte supernatant over control bones supernatant) was assessed using fetal long-bone resorbing assays. Bone resorption was determined by urinary total pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M, compared with Pre-M subjects (1.20 +/- 0.10 and 1.15 +/- 0.20 vs. 0.73 +/- 0.10, respectively, both P < 0.05). Moreover, BRA of bones cultured with the supernatant of Pre-M was lower than BRA of control bones. BRA was significantly correlated with levels of IL-1, IL-6, and tumor necrosis factor-alpha in supernatant. Supernatant IL-1 levels were increased in E-Post-M, compared with Pre-M women (506 +/- 180 vs. 122 +/- 30, P < 0.05). Similarly, pyridinoline levels were increased in E-Post-M and L-Post-M, compared with Pre-M subjects (8.8 +/- 1 and 10.5 +/- 0.9 vs. 5.8 +/- 0.5, respectively, both P < 0.05). BRA was significantly correlated to pyridinoline levels. These data indicate the presence of monocyte activation in L-Post-M, which may be responsible for the increased bone resorption and bone loss observed in this elderly population.

Alcohol, Cytokines, and Estrogen in the Control of Bone Remodeling

Alcohol has been identified as a risk factor for the development of osteoporosis. Chronic alcohol abuse has been shown to decrease bone mass and increase the incidence of fractures. Although the exact mechanism by which alcohol influences bone metabolism is not clear, it is likely a combination of both direct and indirect effects on bone cells. Alcohol has the potential to alter bone metabolism indirectly through its effects on gonadal hormones and through the secretion of cytokines shown to be critical factors in postmeno-pausal osteoporosis. Data are summarized here demonstrating that interleukin-1 and tumor necrosis factor play a direct causal role in the bone loss due to estrogen deficiency. In addition, studies are cited showing that these same cytokines are produced in alcohol-induced liver disease with the potential to enhance bone loss in post-menopausal women and in male patients. Although there are not yet data directly supporting the role of cytokines in bone loss due to alcohol consumption, the studies presented herein are intended to stimulate further research on the role of alcohol, estrogen, and cytokines in osteoporotic bone loss.

Alcohol, cytokines, and estrogen in the control of bone remodeling.

Alcohol has been identified as a risk factor for the development of osteoporosis. Chronic alcohol abuse has been shown to decrease bone mass and increase the incidence of fractures. Although the exact mechanism by which alcohol influences bone metabolism is not clear, it is likely a combination of both direct and indirect effects on bone cells. Alcohol has the potential to alter bone metabolism indirectly through its effects on gonadal hormones and through the secretion of cytokines shown to be critical factors in postmenopausal osteoporosis. Data are summarized here demonstrating that interleukin-1 and tumor necrosis factor play a direct causal role in the bone loss due to estrogen deficiency. In addition, studies are cited showing that these same cytokines are produced in alcohol-induced liver disease with the potential to enhance bone loss in post-menopausal women and in male patients. Although there are not yet data directly supporting the role of cytokines in bone loss due to alcohol consumption, the studies presented herein are intended to stimulate further research on the role of alcohol, estrogen, and cytokines in osteoporotic bone loss.