Disease relevance of Growth Plate

• Mgp-deficient mice additionally exhibit inappropriate calcification of various cartilages, including the growth plate, which eventually leads to short stature, osteopenia and fractures [1].
• Parathyroid hormone-related peptide (PTHrP), synthesized in the periarticular growth plate, regulates the site at which hypertrophy occurs [2].
• E2 (30 nM) caused, within 24 hr, a 70-200% increase in creatine kinase (CK; ATP:creatine N-phosphotransferase, EC 2.7.3.2) specific activity in ROS 17/2.8 rat osteogenic sarcoma cells, MC3T3-E1 mouse calvaria-derived cells, and rat fetal calvaria cells, and a 40% increase in rat epiphyseal cartilage cells [3].
• Spred-2(-/-) mice showed reduced growth and body weight, they had a shorter tibia length, and showed narrower growth plates as compared with wild-type mice [4].
• Histologically, marimastat-treated rat joints were characterized by soft tissue and bone changes, such as increased epiphyseal growth plate, synovial hyperplasia, and increased cellularity in the joint capsule and extracapsular ligaments [5].

Psychiatry related information on Growth Plate

• In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups [6].

High impact information on Growth Plate

• We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse [7].
• Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development [8].
• Growth plates from gelatinase B-null mice in culture show a delayed release of an angiogenic activator, establishing a role for this proteinase in controlling angiogenesis [9].
• MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes [9].
• The results also suggest that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix [10].

Chemical compound and disease context of Growth Plate

• Once-daily oral administration of ZD6474 to growing rats for 14 days produced a dose-dependent increase in the femoro-tibial epiphyseal growth plate zone of hypertrophy, which is consistent with inhibition of VEGF signaling and angiogenesis in vivo [11].
• Compared to saline, growth hormone and insulin treatment significantly enhanced body weights, nose-rump lengths, the widths of the proximal tibia growth plates and the incorporation of sulfate into rib cartilage [12].
• Thyroid hormones (THs), 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine (T4), are important for the normal development of the growth plate (GP); congenital TH deficiency leads to severe dwarfism [13].
• Twenty-four h later in the non-fasting state plasma glucose, insulin, somatomedin activity (porcine assay), body weight, nose-rump length, width of the tibia growth plate, and the 35-S-sulfate incorporation into rib cartilage were determined [12].
• To identify a target for therapy, we want to determine whether estrogen signaling is active in chondrosarcoma because estrogen is important in the regulation of longitudinal growth that is initiated by chondrocyte proliferation and differentiation in the epiphyseal growth plate of long bones [14].

Biological context of Growth Plate

• No differences were detected between the type X collagen-null mice and controls when growth plates of both newborn and 3-week old mice were examined by histology and by immunostaining for extracellular matrix components of bone including osteopontin, osteocalcin and type II collagen [15].
• Recently, we reported that local administration of human GH (hGH) into the proximal cartilage growth plate of the tibia of hypophysectomized rats stimulated longitudinal bone growth on the side injected with the hormone [16].
• Whereas bone length was reduced in Stat5ab(-/-) mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR(-/-) mice, indicating that the effects of GH in bone may not involve Stat5 activation [17].
• Compared with their wild-type littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which is correlated with the activation of Stat proteins and upregulation of cell-cycle inhibitors [18].
• Cotreatment of growth plate chondrocytes with RA and BAPTA-AM, a cell permeable Ca2+ chelator, inhibited the up-regulation of annexin gene expression and mineralization of these cultures [19].

Anatomical context of Growth Plate

• Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro-osseous mineralizing border exhibited expression of both annexin V and type I collagen [20].
• Furthermore, FGF treatment of metatarsal bone rudiments obtained from p107-/-;p130-/- embryos failed to inhibit proliferation of growth plate chondrocytes, whereas rudiments from p107-null or p130-null embryos showed only a slight inhibition of growth [21].
• We have used a catheterization system that permits chronic infusion into the arterial supply of one hindlimb of rats to study the direct effects of rat growth hormone and human somatomedin C on growth of the tibial epiphyseal cartilage plate in hypophysectomized rats [22].
• Histological analysis revealed that GPR103-/- mice exhibited a thinned osteochondral growth plate, a thickening of trabecular branches, and a reduction in osteoclast number, suggestive of an early arrest of osteochondral bone formation [23].
• We report here that Krox-20 is also activated in a subpopulation of growth plate hypertrophic chondrocytes and in differentiating osteoblasts and that its disruption severely affects endochondral ossification [24].

Associations of Growth Plate with chemical compounds

• Radiologic studies and bone histomorphometric analyses showed that phosphate (alone or with ergocalciferol) induced the mineralization of the growth plate but not of the endosteal bone surface [25].
• It has been recognized that receptors for many hormones such as estrogen, GH, and glucocorticoids are present in or on growth plate chondrocytes, suggesting that these hormones may influence processes in the growth plate directly [26].
• Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha [27].
• Homocysteic acid, H03SCH2CH2CHNH2CO2H, promotes growth of hypophysectomized rats, assayed by observation of increased thickness of epiphyseal cartilage of the tibia and by observation of tail growth [28].
• 25-hydroxyvitamin D: autoradiographic evidence of sites of action in epiphyseal cartilage and bone [29].

Gene context of Growth Plate

• In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones [30].
• Using mouse embryos with three or four null alleles of Sox5 and Sox6, we show that they are also essential and redundant in major steps of growth plate chondrocyte differentiation [30].
• Because Sox9 is not expressed in the mineralized portion of the growth plate, this premature mineralization is very likely the consequence of allele insufficiency existing in cells of the growth plate that express Sox9 [31].
• Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification [32].
• Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc(-/-) mice and allow their prolonged survival [33].

Analytical, diagnostic and therapeutic context of Growth Plate

• Northern blotting revealed that the highest levels of TGF-beta mRNA were associated with the growth plates [34].
• Membranes from brefeldin A-treated and untreated chick embryo epiphyseal cartilage were fractionated separately by equilibrium sucrose density gradient centrifugation [35].
• Immunohistochemistry of the fetal bovine growth plate identified a gradient of increasing annexin VIII protein from the proliferative to the hypertrophic zone [36].
• RESULTS: Western blot analysis and RPA showed increased VEGF protein and mRNA expression, respectively, in the epiphyseal cartilage of the infarcted heads compared with the contralateral normal heads [37].
• To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF) [38].

References