scholarly journals Local Changes to the Distal Femoral Growth Plate Following Injury in Mice

2017 ◽  
Vol 139 (7) ◽  
Author(s):  
Lauren M. Mangano Drenkard ◽  
Meghan E. Kupratis ◽  
Katie Li ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan
Keyword(s):  
Growth Plate ◽  
Skeletal Development ◽  
Global Changes ◽  
Mineral Density ◽  
Injury Site ◽  
Hypertrophic Zone ◽  
Proliferative Zone ◽  
Spatial Changes ◽  
Zonal Organization ◽  
Growth Plate Injury

Injury to the growth plate is associated with growth disturbances, most notably premature cessation of growth. The goal of this study was to identify spatial changes in the structure and composition of the growth plate in response to injury to provide a foundation for developing therapies that minimize the consequences for skeletal development. We used contrast-enhanced microcomputed tomography (CECT) and histological analyses of a murine model of growth plate injury to quantify changes in the cartilaginous and osseous tissue of the growth plate. To distinguish between local and global changes, the growth plate was divided into regions of interest near to and far from the injury site. We noted increased thickness and CECT attenuation (a measure correlated with glycosaminoglycan (GAG) content) near the injury, and increased tissue mineral density (TMD) of bone bridges within the injury site, compared to outside the injury site and contralateral growth plates. Furthermore, we noted disruption of the normal zonal organization of the physis. The height of the hypertrophic zone was increased at the injury site, and the relative height of the proliferative zone was decreased across the entire injured growth plate. These results indicate that growth plate injury leads to localized disruption of cellular activity and of endochondral ossification. These local changes in tissue structure and composition may contribute to the observed retardation in femur growth. In particular, the changes in proliferative and hypertrophic zone heights seen following injury may impact growth and could be targeted when developing therapies for growth plate injury.

scholarly journals Effects of bisphosphonates on different zones of the epiphyseal growth plate of rats

2021 ◽  
Vol 10 (14) ◽  
pp. e518101422159
Author(s):  
Deise Ponzoni ◽  
Elissa Kerli Fernandes ◽  
Mateus Muller da Silva ◽  
Izabel Cristina Custódio de Souza ◽  
John Kim Neubert ◽  
...  
Keyword(s):  
Growth Plate ◽  
Histological Analysis ◽  
Skeletal Development ◽  
Fold Increase ◽  
Control Group ◽  
Epiphyseal Growth Plate ◽  
Alendronate Sodium ◽  
Proliferative Zone ◽  
Clinical Disorders ◽  
Plate Cell

Bisphosphonates (BIS) are indicated for several clinical disorders (e.g., osteoporosis). However, BIS has been associated with osteonecrosis and alterations in osteoclastogenesis and skeletal development. This study aimed to evaluate the effects of BIS (zoledronic acid - ZA and alendronate sodium - AS) on zones of the growth plate of rat femur. Animals (Wistar rats, n = 19) were divided into groups: 1) AS Group: animals received alendronate sodium orally (3 mg/kg per day); 2) ZA Group: ZA was administered intraperitoneally (0.2 mg/kg per week); and 3) Control Group (CG): a vehicle was administered. Animals were euthanized 21 days after the treatment, and femurs were collected for histological analysis. The images of all zones (resting, proliferative, hypertrophic, and calcified) were processed by the Qcapture® software providing a 40 and 400-fold increase.  ZA decreased epiphyseal growth plate cell zones (ZA Group vs. CG) in most cases. Likewise, AS diminished the proliferative zone (AS Group vs. CG). Furthermore, ZA increased the calcified zone (ZA Group vs. CG). Previous works demonstrated that BIS decrease the epiphyseal disc. This reduction is probably due to the shortening of the cellular zones that undergoes calcification/ossification. The present results suggest that BIS should be carefully indicated because these drugs might accelerate epiphyseal closure.

scholarly journals The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage

2014 ◽  
Vol 221 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Rosa Chung ◽  
Bruce K Foster ◽  
Cory J Xian
Keyword(s):  
Blood Vessel ◽  
Growth Plate ◽  
Bone Growth ◽  
Fracture Repair ◽  
Bone Lengthening ◽  
Bony Tissue ◽  
Injury Site ◽  
Repair Tissue ◽  
Anti Vegf ◽  
Growth Plate Injury

Growth plate injuries often result in undesirable bony repair causing bone growth defects, for which the underlying mechanisms are unclear. Whilst the key importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well-known in bone development and fracture repair, its role during growth plate bony repair remains unexplored. Using a rat tibial growth plate injury repair model with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5 mg/kg) after injury, this study examined the roles of VEGF-driven angiogenesis during growth plate bony repair. Histology analyses observed isolectin-B4-positive endothelial cells and blood vessel-like structures within the injury site on days 6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like structures within the injury site (P<0.05). Compared with untreated controls, anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal repair tissue, but decreased bony tissue at the injury site at day 14 (P<0.01). Consistently, microcomputed tomography analysis of the injury site showed significantly decreased bony repair tissue after treatment (P<0.01). RT-PCR analyses revealed a significant decrease in osteocalcin (P<0.01) and a decreasing trend in Runx2 expression at the injury site following treatment. Furthermore, growth plate injury-induced reduced tibial lengthening was more pronounced in anti-VEGF-treated injured rats on day 60, consistent with the observation of a significantly increased height of the hypertrophic zone adjacent to the growth plate injury site (P<0.05). These results indicate that VEGF is important for angiogenesis and formation of bony repair tissue at the growth plate injury site as well as for endochondral bone lengthening function of the uninjured growth plate.

scholarly journals The Somatostatin Analog Octreotide Inhibits GH-Stimulated, But Not IGF-I-Stimulated, Bone Growth in Hypophysectomized Rats

Endocrinology ◽  
2002 ◽  
Vol 143 (8) ◽  
pp. 2944-2952 ◽  
Author(s):  
Jürgen Zapf ◽  
Martina Gosteli-Peter ◽  
Gisbert Weckbecker ◽  
Ernst B. Hunziker ◽  
Manfred Reinecke
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Body Weight Gain ◽  
Somatostatin Analog ◽  
Hypertrophic Zone ◽  
Gh Secretion ◽  
Proliferative Zone ◽  
Igf I ◽  
Hypophysectomized Rats ◽  
Tibial Epiphyseal

Abstract IGF-I mediates growth-promoting actions of GH. In the present study we investigated whether the somatostatin analog octreotide blunts the stimulatory effects of GH and/or IGF-I on bone growth in hypophysectomized rats infused for 6 d with vehicle, GH, or IGF-I. 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%). Furthermore, octreotide significantly reduced the GH-induced increase in the number of IGF-I immunoreactive chondrocytes in all layers (except in the upper hypertrophic zone) of the tibial growth plate cartilage (P &lt; 0.0001 for stem cell and proliferative zone; P &lt; 0.0005 for lower hypertrophic zone). These findings demonstrate that octreotide does not interfere with IGF-I action, but does interfere with local GH-stimulated IGF-I production in the growth plate. Thus, besides inhibiting pituitary GH secretion, octreotide exerts inhibitory peripheral effects on GH-stimulated longitudinal bone growth.

scholarly journals Post-Traumatic Caspase-3 Expression in the Adjacent Areas of Growth Plate Injury Site: A Morphological Study

2013 ◽  
Vol 14 (8) ◽  
pp. 15767-15784 ◽  
Author(s):  
Giuseppe Musumeci ◽  
Paola Castrogiovanni ◽  
Carla Loreto ◽  
Sergio Castorina ◽  
Karin Pichler ◽  
...  
Keyword(s):  
Growth Plate ◽  
Morphological Study ◽  
Caspase 3 ◽  
Injury Site ◽  
Post Traumatic ◽  
Growth Plate Injury

scholarly journals Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

2002 ◽  
Vol 173 (3) ◽  
pp. 407-414 ◽  
Author(s):  
O Nilsson ◽  
V Abad ◽  
D Chrysis ◽  
EM Ritzen ◽  
L Savendahl ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Postnatal Development ◽  
Growth Plate ◽  
Estrogen Receptor Alpha ◽  
Proximal Tibia ◽  
Distal Humerus ◽  
Receptor Alpha ◽  
Hypertrophic Zone ◽  
Proliferative Zone ◽  
Epiphyseal Fusion

Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ERalpha and ERbeta was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ERalpha and ERbeta are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.

scholarly journals Loss of Wnt16 Leads to Skeletal Deformities and Downregulation of Bone Developmental Pathway in Zebrafish

2021 ◽  
Vol 22 (13) ◽  
pp. 6673
Author(s):  
Xiaochao Qu ◽  
Mei Liao ◽  
Weiwei Liu ◽  
Yisheng Cai ◽  
Qiaorong Yi ◽  
...  
Keyword(s):  
Gene Knockout ◽  
Integration Site ◽  
Skeletal Development ◽  
Rna Seq ◽  
Developmental Pathway ◽  
Mineral Density ◽  
Zebrafish Model ◽  
Protein Protein Interaction ◽  
Ct Analysis

Wingless-type MMTV integration site family, member 16 (wnt16), is a wnt ligand that participates in the regulation of vertebrate skeletal development. Studies have shown that wnt16 can regulate bone metabolism, but its molecular mechanism remains largely undefined. We obtained the wnt16-/- zebrafish model using the CRISPR-Cas9-mediated gene knockout screen with 11 bp deletion in wnt16, which led to the premature termination of amino acid translation and significantly reduced wnt16 expression, thus obtaining the wnt16-/- zebrafish model. The expression of wnt16 in bone-related parts was detected via in situ hybridization. The head, spine, and tail exhibited significant deformities, and the bone mineral density and trabecular bone decreased in wnt16-/- using light microscopy and micro-CT analysis. RNA sequencing was performed to explore the differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the down-regulated DEGs are mainly concentrated in mTOR, FoxO, and VEGF pathways. Protein–protein interaction (PPI) network analysis was performed with the detected DEGs. Eight down-regulated DEGs including akt1, bnip4, ptena, vegfaa, twsg1b, prkab1a, prkab1b, and pla2g4f.2 were validated by qRT-PCR and the results were consistent with the RNA-seq data. Overall, our work provides key insights into the influence of wnt16 gene on skeletal development.

An ultrastructural study of mitotic chondrocytes in the proliferative zone of the rat tibial growth plate

1993 ◽  
Vol 175 (1) ◽  
pp. 41-45 ◽  
Author(s):  
S. Shibata ◽  
O. Baba ◽  
M. Niikura ◽  
S. Suzuki ◽  
Y. Yamashita ◽  
...  
Keyword(s):  
Growth Plate ◽  
Ultrastructural Study ◽  
Proliferative Zone ◽  
Tibial Growth Plate

scholarly journals Bone Mineral Density in Children From Anthropological and Clinical Sciences: A Review

2014 ◽  
Vol 77 (2) ◽  
pp. 111-135 ◽  
Author(s):  
Bernadette M. Manifold
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Skeletal Development ◽  
Quantitative Computed Tomography ◽  
Childhood And Adolescence ◽  
Mineral Density ◽  
Clinical Literature ◽  
Adults And Children ◽  
Future Potential ◽  
Anthropological Literature

Abstract Bone mineral density (BMD) is a frequent topic of discussion in the clinical literature in relation to the bone health of both adults and children. However, in archaeological and/ or anthropological studies the role of BMD is often cited as a possible factor in the poor skeletal preservation which can lead to an under-representation of juvenile skeletal remains. During skeletal development and growth throughout childhood and adolescence changes take place in both the size and shape of bones and these changes also result in the increasing of mineral content. BMD can be affected by many factors, which include, age, genetics, sexual maturation, amount of physical activity and dietary calcium. This paper aims to review the clinical and anthropological literature on BMD and discuss the numerous methods of measurement and how the availability of certain methods such as Dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT) can influence the study of bone density in archaeological skeletal collections and also the future potential for forensic anthropological studies.

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