Disease relevance of Bone Development

• We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth [1].
• These data suggest that PGHS-2 is not necessary for wild-type bone development but plays a critical role in bone resorption stimulated by 1,25-D and PTH [2].
• Three hundred micrograms (39 nmol) of rhIGF-I per day and 200 milliunits (4.5 nmol) of human growth hormone (hGH) per day increased body weight, tibial epiphyseal width, longitudinal bone growth, and trabecular bone formation similarly [3].
• In addition to deaths associated with expression in neurons and keratinized epithelia, bovine oncostatin M caused abnormalities in bone growth and spermatogenesis, stimulated fibrosis surrounding islets in the pancreas, and disrupted normal lymphoid tissue development [4].
• These data suggest that Igf1 promotes longitudinal bone growth by 'insulin-like' anabolic actions which augment chondrocyte hypertrophy [5].

Psychiatry related information on Bone Development

• This study examined the possibility that maternal alcohol consumption may affect fetal bone development by altering fetal levels of parathyroid hormone (PTH), 1,25(OH)2D, or calcitonin (hormones that regulate calcium (Ca) and bone metabolism in the adult animal) [6].

High impact information on Bone Development

• Recently, some of the in vivo targets and mechanisms leading to changes in neuronal adaptation, smooth muscle relaxation and growth, intestinal water secretion, bone growth, renin secretion, and other important functions have been identified [7].
• This decade also saw the description of a male patient who had no functional ER alpha and whose continued bone growth clearly revealed an important function of estrogen in men [8].
• Cbfbeta interacts with Runx2 and has a critical role in bone development [9].
• The fusion allele maintains sufficient function in hematopoietic cells to bypass the early embryonic lethality, and identifies a new role for Cbfb in bone development [9].
• Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation [10].

Chemical compound and disease context of Bone Development

• Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal [11].
• The administration of ArGHS, but not normal goat serum, caused a dose-dependent decrease in body weight gain and longitudinal bone growth, as measured by the tetracycline method [12].
• Treatment with IGF-I had no effect on plasma glucose levels, body weight, or longitudinal bone growth [13].
• We found that octreotide significantly suppressed the GH-induced rise in liver IGF-I mRNA (-27%) and peptide (-32%) and the serum IGF-I level (-26%) and concomitantly inhibited GH-stimulated, but not IGF-I-stimulated, body weight gain (-31%), tibial epiphyseal width (-14%), and bone growth rate (-24%) [14].
• Pamidronate [aminohydroxypropylidene diphosphonate disodium (APD), disodium pamidronate] is an orally and intravenously active amino-substituted bisphosphonate which produces potent and specific inhibition of bone resorption at doses devoid of any significant detrimental effect on bone growth and mineralisation [15].

Biological context of Bone Development

• The time-dependent accumulation of TGF beta when cartilage is being replaced by bone in this in vivo model of bone formation suggests that TGF beta may play a role in the regulation of ossification during endochondral bone development [16].
• Apparent PTHrP functions include the regulation of endochondral bone development, of hair follicle formation, and of branching morphogenesis in the breast [17].
• These results support the concept that growth hormone stimulates long bone growth by inducing local production of somatomedin, which in turn stimulates cell proliferation in an autocrine or paracrine fashion [18].
• The core binding factor beta subunit (CBF beta) is the non-DNA binding subunit of the core-binding factors, transcription factors essential for multiple developmental processes including hematopoiesis and bone development [19].
• These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development [20].

Anatomical context of Bone Development

• These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation [21].
• Fgf18 is expressed in both osteogenic mesenchymal cells and differentiating osteoblasts during calvarial bone development [22].
• Since IGF-I is involved in normal bone growth and differentiation, we have evaluated the possible role of IGF-I signaling in the growth of human osteogenic sarcoma cell lines [23].
• We provide in vivo evidence that TGFbeta signaling within the CNC-derived dura mater provides essential inductive instruction for both the CNC- and mesoderm-derived calvarial bone development [24].
• Taken together, our findings indicate that STC1 inhibits longitudinal bone growth directly at the growth plate [25].

Associations of Bone Development with chemical compounds

• Daily injections of a partially purified somatomedin preparation failed to induce accumulated longitudinal bone growth using the intravital marker tetracycline or by measuring the nose-to-tail length [26].
• Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth [27].
• Calcitriol but no other metabolite of vitamin D is essential for normal bone growth and development in the rat [28].
• Collectively, the data indicate that neither calcidiol nor any 24-hydroxylated metabolite of calcidiol is needed in the rat (other than as a precursor) for longitudinal or transverse bone growth, for normal endochondral ossification, or for normal periosteal and endosteal formation, mineralization, and resorption of bone [28].
• Osteopontin is a phosphorylated glycoprotein secreted to the mineralizing extracellular matrix by osteoblasts during bone development [29].

Gene context of Bone Development

• Postnatal growth curves indicated that surviving Igf-1(-/-) mutants, which are infertile and exhibit delayed bone development, continue to grow with a retarded rate after birth in comparison with wild-type littermates and become 30% of normal weight as adults [30].
• Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development [31].
• These results define a new mouse osteopetrotic mutant and implicate NF-kappaB proteins in bone development, raising new directions in the treatment of bone disorders [32].
• PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth [33].
• In calvarial bone development of Fgf18-deficient mice generated by gene targeting, the progress of suture closure is delayed [22].

Analytical, diagnostic and therapeutic context of Bone Development

• Longitudinal studies showed that Sca-1(-/-) mice undergo normal bone development but with age exhibit dramatically decreased bone mass resulting in brittle bones [34].
• To study the function of FGFR3 in bone growth and to create animal models for the FGFR3-related inherited skeletal disorders, we introduced a point mutation (Lys644Glu) into the murine FGFR3 genome using a knock-in approach [35].
• In our study, we used an organ culture system to evaluate the effects of STC on growth plate chondrogenesis, which is the primary determinant of longitudinal bone growth [25].
• Comprehensive microarray analysis of bone morphogenetic protein 2-induced osteoblast differentiation resulting in the identification of novel markers for bone development [36].
• The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells [37].

References