Disease relevance of Bone Remodeling

• Our results suggest that TGF-beta 2 functions as a local positive regulator of bone remodeling and that alterations in TGF-beta 2 synthesis by bone cells, or in their responsiveness to TGF-beta 2, may contribute to the pathogenesis of metabolic bone disease [1].
• These data suggest that bone disease in these subjects is not due to inhibition of parathyroid hormone secretion or function, or abnormal vitamin D metabolism, but to an inhibition of bone remodeling by a mechanism independent of the calciotropic hormones [2].
• Our findings indicate that sclerostin plays an important role in bone remodeling and links bone resorption and bone apposition [3].
• Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses [4].
• The chronic excessive hypersecretion of parathyroid hormone (PTH) in primary hyperparathyroidism (PHPT) has significant impact on bone remodeling [5].

Psychiatry related information on Bone Remodeling

• There was a marked reduction in bone remodeling markers, serum osteocalcin, and the ratio of urinary cross-linked N:-telopeptides of type 1 collagen to creatinine with alcohol consumption, suggesting that increased BMD with alcohol consumption could be due to reduced bone remodeling [6].
• These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group, beyond its suppressive effect on iPTH [7].

High impact information on Bone Remodeling

• The TNF-family molecule RANK-L (RANK-L, TRANCE, ODF) and its receptor RANK are key regulators of bone remodeling, and they are essential for the development and activation of osteoclasts [8].
• The hormone leptin is a regulator of bone remodeling, a homeostatic function maintaining bone mass constant [9].
• Osteoprotegerin-ligand (OPGL) is a key osteoclast differentiation/activation factor essential for bone remodeling [10].
• Receptor activator of NF-kappaB (RANK) and its ligand RANKL have been identified as essential factors involved in osteoclast development and bone remodeling, but their mechanism and interacting factors have not been fully characterized [11].
• In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I [12].

Chemical compound and disease context of Bone Remodeling

• CONCLUSION: Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women [13].
• Osteopenia and bone-remodeling abnormalities in warfarin-treated lambs [14].
• Cyclosporine bone remodeling effect prevents steroid osteopenia after kidney transplantation [15].
• Cyclosporin A increases the biochemical markers of bone remodeling in primary biliary cirrhosis [16].
• Nitric oxide (NO) inhibits osteoclastic bone resorption in vitro and regulates bone remodeling in vivo [17].

Biological context of Bone Remodeling

• Recent studies have revealed that OPN plays critical roles in bone remodeling and cell-mediated immunity [18].
• Carbonic anhydrase II (CAII), found in renal tubules, brain, and osteoclasts, is critical in acid-base homeostasis and bone remodeling [19].
• Contributing to this progress is the elegant work on c-fos, where Wagner and coworkers identify this proto-oncogene as a primary factor which directs cell differentiation along the osteoclast/macrophage lineages, and thus regulates bone remodeling [20].
• This phenotype implicates TGF-beta2 as a physiological regulator of bone remodeling and raises the question of how this single secreted factor regulates the functions of osteoblasts and osteoclasts and coordinates their opposing activities in vivo [21].
• The serum glycoprotein fetuin is expressed during embryogenesis in multiple tissues including limb buds and has been shown to promote bone remodeling and stimulate cell proliferation in vitro [22].

Anatomical context of Bone Remodeling

• Monocyte recruitment and expression of monocyte chemoattractant protein-1 are developmentally regulated in remodeling bone in the mouse [23].
• To elucidate the in vivo effect of OSM on bone remodeling, we injected an adenoviral vector encoding murine OSM in knee joints of mice [24].
• Because IL-1 is a potent regulator in bone remodeling, we examined whether IL-1 beta induces JE expression in a clonal mouse osteoblastic cell line, MC3T3-E1 [25].
• In bone from pycnodysostotic patients and cathepsin K-deficient mice, conditions in which osteoclastic bone matrix digestion is greatly inhibited, bone matrix leftovers proved to be degraded by bone lining cells, thus indicating that the bone lining cell "rescues" bone remodeling in these anomalies [26].
• These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF [27].

Associations of Bone Remodeling with chemical compounds

• This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling [28].
• Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling [29].
• CONTEXT: Ingestion of toxic amounts of vitamin A affects bone remodeling and can have adverse skeletal effects in animals [30].
• There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling [31].
• To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6(+/+)) or IL-6 gene knockout (il6(-/-)) mice that were fed either control or ethanol liquid diets for 4 months [32].

Gene context of Bone Remodeling

• In the present study, we demonstrate a novel function of the Stat1 transcription factor in the regulation of bone remodeling [33].
• Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro [34].
• We now report that transforming growth factor beta1 (TGF-beta1), a potent regulatory cytokine of bone remodeling, is a powerful stimulator for gene expression of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in osteoblastic MC3T3-E1 cells [35].
• These findings suggest that PDGF and IL-1 are jointly involved in the bone-remodeling microenvironment as local coupling factors [36].
• Taken together, these findings define novel mechanisms involving the intersection of three pathways, Runx2, 1,25(OH)(2)D(3), and Notch signaling, that play a major role in the regulation of OPN in osteoblastic cells and therefore in the process of bone remodeling [37].

Analytical, diagnostic and therapeutic context of Bone Remodeling

• Strikingly, ovariectomy does not induce any change in either bone mass or bone remodeling rates in the IL-6 deficient mice [38].
• To define further CSF-1's role in bone remodeling, we examined the effect of neutralizing antisera to CSF-1 on basal and parathyroid hormone (PTH)-induced bone resorption using two organ culture assays designed to examine the recruitment of osteoclast precursors and the activation of mature osteoclasts, respectively [39].
• The purpose of this study was to document the effects of aminobutane bisphosphonate (AHBuP) on bone remodeling during immobilization in rats [40].
• Multifactorial low remodeling bone disease during cyclic total parenteral nutrition [41].
• The pattern of changes in human bone remodeling produced by raloxifene (60 mg/day) was compared to that of estrogen (given as hormone replacement therapy) in 33 early postmenopausal women randomly assigned to raloxifene, estrogen, or no treatment [42].

References