Disease relevance of Osteogenesis

• We provide evidence for direct effects of TSH on both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption, mediated via the TSH receptor (TSHR) found on osteoblast and osteoclast precursors [1].
• BACKGROUND: Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain [2].
• METHODS: In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta, we administered pamidronate intravenously (mean [+/-SD] dose, 6.8+/-1.1 mg per kilogram of body weight per year) at 4-to-6-month intervals for 1.3 to 5.0 years [2].
• Even a 50% reduction in TSHR expression produces profound osteoporosis (bone loss) together with focal osteosclerosis (localized bone formation) [1].
• These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions [3].

Psychiatry related information on Osteogenesis

• CONCLUSION: Painful diffuse osteosclerosis can follow intravenous drug abuse and is possibly caused by parenteral transmission of a virus that in some way stimulates bone formation [4].
• In the presence of estrogen deficiency, the stimulus of physical activity is thought first to decrease the rate of turnover and secondly to increase bone formation [5].
• Effects of parathyroid hormone on bone formation in a rat model for chronic alcohol abuse [6].
• Perhaps MECP2 mutations in Rett syndrome not only influence brain development but also affect bone formation [7].
• While initial findings identified NPY is an important contributor to the regulation of feeding, body weight and blood pressure, more recent work as revealed more subtle functions of this peptide and its potential role in affective disorders, bone formation and cravings [8].

High impact information on Osteogenesis

• Human and mouse genetic and in vitro evidence has shown that canonical Wnt signaling promotes bone formation, but we found that mice lacking the canonical Wnt antagonist Dickkopf2 (Dkk2) were osteopenic [9].
• A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse [10].
• The molecular clock mediates leptin-regulated bone formation [11].
• These cells do, however, express Runx2/Cbfa1, another transcription factor required for bone formation [12].
• In Osx null mice, no bone formation occurs [12].

Chemical compound and disease context of Osteogenesis

• Thus, the increased bone resorption, which is a consequence of estrogen-deficiency, entrains increased bone formation, which masks a simultaneous reduction in estrogen-dependent bone formation [13].
• Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce bone resorption and turnover [14].
• Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption [15].
• Urinary hydroxyproline (r = 0.29, P less than 0.001), an index of bone resorption, and serum alkaline phosphatase (r = 0.31, P less than 0.001), an index of bone formation, also increased with age and these increases correlated with increases in serum BGP (r = 0.39, P less than 0.001 and r = 0.43, P less than 0.001, respectively) [16].
• Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss [17].

Biological context of Osteogenesis

• 1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily [18].
• These results demonstrate that src is not required for general cell viability (possibly because of functional overlap with other tyrosine kinases related to src) and uncover an essential role for src in bone formation [19].
• Analysis of embryonic Cbfa1 expression using a lacZ reporter gene revealed strong expression at sites of bone formation prior to the earliest stages of ossification [20].
• The BMP-7-binding affinity of site-specific variants of Noggin is correlated with alterations in bone formation and apoptosis in chick limb development, showing that Noggin functions by sequestering its ligand in an inactive complex [21].
• TGF-beta 2 is involved in wound healing, bone formation and modulation of immune functions [22].

Anatomical context of Osteogenesis

• The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation [12].
• Leptin regulates bone formation via the sympathetic nervous system [23].
• CONCLUSIONS: Overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes is associated with the disabling ectopic osteogenesis of fibrodysplasia ossificans progressiva [24].
• This study identifies leptin as a potent inhibitor of bone formation acting through the central nervous system and therefore describes the central nature of bone mass control and its disorders [25].
• Thus, VEGF is an essential coordinator of chondrocyte death, chondroclast function, extracellular matrix remodeling, angiogenesis and bone formation in the growth plate [26].

Associations of Osteogenesis with chemical compounds

• In contrast, the dynamic measurements, determined with tetracycline markers, showed that the mean rate of bone formation in the blacks was only 35 percent of that in the whites (P less than 0.001) [27].
• Cyclic administration of pamidronate in children with severe osteogenesis imperfecta [2].
• Microradiography and videodensitometry studies revealed significant increases in bone formation (P less than 0.01) and bone mass (P less than 0.005) in the fluoride-calcium group [28].
• We conclude that aluminum deposition is associated with impaired bone formation or mineralization and with a poor response to calcitriol therapy [29].
• To ascertain if the features of osteogenesis imperfecta could be due to an abnormality in two genetically distinct collagens, Type III and Type I, we measured, in pepsin digests of skin, the ratio of the alpha 1, (III) to alpha 1 (I) chains derived from the two types, using a method of interrupted polyacrylamide-gel electrophoresis [30].

Gene context of Osteogenesis

• Msx2-/- mice also have defects in endochondral bone formation [31].
• NFAT and Osterix cooperatively regulate bone formation [32].
• In fact, bone formation is inhibited in Nfatc1- and Nfatc2-deficient cells as well as in FK506-treated osteoblasts [32].
• The critical components of this extract, termed bone morphogenetic protein (BMP), that direct cartilage and bone formation as well as the constitutive elements supplied by the animal during this process have long remained unclear [33].
• A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now been isolated [34].

Analytical, diagnostic and therapeutic context of Osteogenesis

• These changes were accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, as determined by ex vivo bone marrow cell cultures [35].
• Consistent with these data, addition of IL-7 to neonatal calvarial organ cultures blocked new bone formation, and injection of IL-7 into mice in vivo inhibited bone formation as measured by calcein incorporation into long bones [36].
• Gene targeting shows that core-binding factor alpha 1 (Cbfa1) plays an essential role in bone formation and osteoblast differentiation [37].
• In contrast to the delayed expression of TGF beta protein, northern blot analysis showed TGF beta mRNA in implants throughout the sequence of bone formation [38].
• Gel filtration of the 4 M guanidine HCl extract of fine powder on Sepharose CL-6B and the subsequent reconstitution of various column fractions with inactive coarse residue showed that fractions with proteins of 20,000-50,000 mol wt induced new bone formation [39].

References