scholarly journals Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development

2022 ◽  
Author(s):  
Subburaman Mohan ◽  
Gustavo A Gomez ◽  
Patrick Aghajanian ◽  
Sheila Pourteymoor ◽  
Destiney Larkin
Keyword(s):  
Thyroid Hormone ◽  
Soft Tissues ◽  
Distal Femur ◽  
Weight Bearing ◽  
Ossification Center ◽  
Cartilage Calcification ◽  
Chondrocyte Maturation ◽  
Distal Epiphysis ◽  
Secondary Ossification Center

The proximal and distal femur epiphysis of mice are both weight bearing structures derived from chondrocytes but differ in development. Mineralization at the distal epiphysis occurs in an osteoblast rich secondary ossification center (SOC), while the chondrocytes of the proximal femur head (FH) in particular, are directly mineralized. Thyroid hormone (TH) plays important roles in distal knee SOC formation, but whether TH also affects proximal FH development remains unexplored. Here, we found that TH controls chondrocyte maturation and mineralization at the FH in vivo through studies in Thyroid stimulating hormone receptor (Tshr -/-) hypothyroid mice by X-ray, histology, transcriptional profiling, and immunofluorescence staining. Both in vivo, and in vitro studies conducted in ATDC5 chondrocyte progenitors concur that TH regulates expression of genes that modulate mineralization (Bsp, Ocn, Dmp1, Opn, and Alp). Our work also delineates differences in prominent transcription factor regulation of genes involved in the different mechanisms leading to proximal FH cartilage calcification and endochondral ossification at the distal femur. The information on the molecular pathways contributing to postnatal cartilage calcification can provide insights on therapeutic strategies to treat pathological calcification that occurs in soft tissues such as aorta, kidney, and articular cartilage.

scholarly journals Skeletal defects in VEGF120/120 mice reveal multiple roles for VEGF in skeletogenesis

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1893-1904 ◽  
Author(s):  
Elazar Zelzer ◽  
William McLean ◽  
Yin-Shan Ng ◽  
Naomi Fukai ◽  
Anthony M. Reginato ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Skeletal Development ◽  
Surrounding Tissue ◽  
Ossification Center ◽  
Direct Role ◽  
Osteoblastic Activity ◽  
Chondrocyte Maturation ◽  
Skeletal Defects

Angiogenesis is an essential component of skeletal development and VEGF signaling plays an important if not pivotal role in this process. Previous attempts to examine the roles of VEGF in vivo have been largely unsuccessful because deletion of even one VEGF allele leads to embryonic lethality before skeletal development is initiated. The availability of mice expressing only the VEGF120 isoform (which do survive to term) has offered an opportunity to explore the function of VEGF during embryonic skeletal development. Our study of these mice provides new in vivo evidence for multiple important roles of VEGF in both endochondral and intramembranous bone formation, as well as some insights into isoform-specific functions. There are two key differences in vascularization of developing bones between wild-type and VEGF120/120 mice. VEGF120/120 mice have not only a delayed recruitment of blood vessels into the perichondrium but also show delayed invasion of vessels into the primary ossification center, demonstrating a significant role of VEGF at both an early and late stage of cartilage vascularization. These findings are the basis for a two-step model of VEGF-controlled vascularization of the developing skeleton, a hypothesis that is supported by the new finding that VEGF is expressed robustly in the perichondrium and surrounding tissue of cartilage templates of future bones well before blood vessels appear in these regions. We also describe new in vivo evidence for a possible role of VEGF in chondrocyte maturation, and document that VEGF has a direct role in regulating osteoblastic activity based on in vivo evidence and organ culture experiments.

scholarly journals Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor

2012 ◽  
Vol 303 (12) ◽  
pp. E1489-E1501 ◽  
Author(s):  
Dibyendu Kumar Panda ◽  
David Goltzman ◽  
Andrew C. Karaplis
Keyword(s):  
Parathyroid Hormone ◽  
Transgenic Mice ◽  
Growth Plate ◽  
Ossification Center ◽  
Newborn Mouse ◽  
Differentiation Markers ◽  
Altered Expression ◽  
Chondrocyte Maturation

The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

Biological and biomedical applications of collagenous biomaterials

1990 ◽  
Vol 48 (3) ◽  
pp. 856-857
Author(s):  
Yasushi P. Kato ◽  
Michael G. Dunn ◽  
Frederick H. Silver ◽  
Arthur J. Wasserman
Keyword(s):  
Biomedical Applications ◽  
Soft Tissues ◽  
Collagen Fibers ◽  
Bone Collagen ◽  
Cover Slip ◽  
Fibroblast Migration ◽  
Cellular Expression ◽  
Defect Repair

Collagenous biomaterials have been used for growing cells in vitro as well as for augmentation and replacement of hard and soft tissues. The substratum used for culturing cells is implicated in the modulation of phenotypic cellular expression, cellular orientation and adhesion. Collagen may have a strong influence on these cellular parameters when used as a substrate in vitro. Clinically, collagen has many applications to wound healing including, skin and bone substitution, tendon, ligament, and nerve replacement. In this report we demonstrate two uses of collagen. First as a fiber to support fibroblast growth in vitro, and second as a demineralized bone/collagen sponge for radial bone defect repair in vivo.For the in vitro study, collagen fibers were prepared as described previously. Primary rat tendon fibroblasts (1° RTF) were isolated and cultured for 5 days on 1 X 15 mm sterile cover slips. Six to seven collagen fibers, were glued parallel to each other onto a circular cover slip (D=18mm) and the 1 X 15mm cover slip populated with 1° RTF was placed at the center perpendicular to the collagen fibers. Fibroblast migration from the 1 x 15mm cover slip onto and along the collagen fibers was measured daily using a phase contrast microscope (Olympus CK-2) with a calibrated eyepiece. Migratory rates for fibroblasts were determined from 36 fibers over 4 days.

A Comparative Study of the in vivo Distribution of 32P-Polyphosphates and 32P-Orthophosphate

1972 ◽  
Vol 11 (01) ◽  
pp. 70-78
Author(s):  
Esther Miller ◽  
Leopoldo Anghileri
Keyword(s):  
Radiation Dose ◽  
Comparative Study ◽  
Soft Tissues ◽  
Tumor Bearing ◽  
In Vivo Distribution ◽  
The Cross ◽  
Total Body

SummaryThe distribution of 32P-polyphosphates (lineal and cross-linked) and 32Porthophosphate in normal and tumor bearing animals has been studied. Differences between the cross-linked and the lineal form are related to a different degree of susceptibility to the hydrolysis by the phosphatases. In contrast to orthophosphate, the polyphosphates showed a lower accumulation in soft tissues which gives an advantageous reduction of the total body radiation dose.

scholarly journals Ultra-strong bio-glue from genetically engineered polypeptides

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chao Ma ◽  
Jing Sun ◽  
Bo Li ◽  
Yang Feng ◽  
Yao Sun ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Covalent Bond ◽  
Genetically Engineered ◽  
Supramolecular Interactions ◽  
Molar Ratio ◽  
High Adhesion ◽  
Strong Adhesion ◽  
Order Of Magnitude

AbstractThe development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.

scholarly journals Supracondylar rotation osteotomy of the femur influences the coronal alignment of the ankle

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Christian Konrads ◽  
Marc-Daniel Ahrend ◽  
Myriam R. Beyer ◽  
Ulrich Stöckle ◽  
Sufian S. Ahmad
Keyword(s):  
Subtalar Joint ◽  
Distal Femur ◽  
External Rotation ◽  
Weight Bearing ◽  
Orientation Angle ◽  
Osteotomy Site ◽  
Limb Alignment ◽  
Coronal Alignment ◽  
Rotational Osteotomy ◽  
Rotation Osteotomy

Abstract Purpose Osteotomies represent well-established treatment-options for the redistribution of loads and forces within and around the knee-joint. Effects of these osteotomies on the remaining planes and adjacent joints are not fully understood. The aim of this study was to determine the influence of a distal-femoral-rotation-osteotomy on the coronal alignment of the ankle. It was hypothesized that supracondylar-external-rotation-osteotomy of the distal femur leads to a change in the coronal orientation of the ankle joint. Methods Long-leg standing radiographs and CT-based torsional measurements of 27 patients undergoing supracondylar-rotational-osteotomy of the femur between 2012 and 2019 were obtained and utilized for the purpose of this study. Postoperative radiographs were obtained after union at the osteotomy-site. The hip-knee-ankle-angle (HKA), the mechanical-lateral-distal-femur-angle (mLDFA), and Tibia-Plafond-Horizontal-Orientation-Angle (TPHA) around the ankle were measured. Comparison between means was performed using the Wilcoxon-Mann–Whitney test. Results Twenty-seven patients with high femoral antetorsion (31.3° ± 4.0°) underwent supracondylar-external-rotation-osteotomy. The osteotomy led to a reduced antetorsion (17.4 ± 5.1; p < 0.001) and to a valgisation of the overall limb-alignment. The HKA decreased by 2.4° ± 1.4° (p < 0.001). The TPHA decreased by 2.6° (p < 0.001). Conclusions Supracondylar external rotation osteotomy of the femur leads to lateralization of the weight bearing line at the knee and ankle due to valgisation of the coronal limb alignment. The mobile subtalar joint has to compensate (inversion) for the resulting valgus orientation of the ankle to ensure contact between the foot and the floor. When planning a rotational osteotomy of the lower limb, this should be appreciated – especially in patients with a preexisting valgus alignment of the lower extremities or restricted mobility in the subtalar joint.

scholarly journals The Potential of Calcium/Phosphate Containing MAO Implanted in Bone Tissue Regeneration and Biological Characteristics

2021 ◽  
Vol 22 (9) ◽  
pp. 4706
Author(s):  
Shun-Yi Jian ◽  
Salim Levent Aktug ◽  
Hsuan-Ti Huang ◽  
Cheng-Jung Ho ◽  
Sung-Yen Lin ◽  
...  
Keyword(s):  
Corrosion Resistance ◽  
Calcium Phosphate ◽  
Soft Tissues ◽  
Salt Spray ◽  
Surface Characteristics ◽  
Corrosion Current ◽  
Biological Properties ◽  
Bone Tissue Regeneration ◽  
Additional Surgery

Micro arc oxidation (MAO) is a prominent surface treatment to form bioceramic coating layers with beneficial physical, chemical, and biological properties on the metal substrates for biomaterial applications. In this study, MAO treatment has been performed to modify the surface characteristics of AZ31 Mg alloy to enhance the biocompatibility and corrosion resistance for implant applications by using an electrolytic mixture of Ca3(PO4)2 and C10H16N2O8 (EDTA) in the solutions. For this purpose, the calcium phosphate (Ca-P) containing thin film was successfully fabricated on the surface of the implant material. After in-vivo implantation into the rabbit bone for four weeks, the apparent growth of soft tissues and bone healing effects have been documented. The morphology, microstructure, chemical composition, and phase structures of the coating were identified by SEM, XPS, and XRD. The corrosion resistance of the coating was analyzed by polarization and salt spray test. The coatings consist of Ca-P compounds continuously have proliferation activity and show better corrosion resistance and lower roughness in comparison to mere MAO coated AZ31. The corrosion current density decreased to approximately 2.81 × 10−7 A/cm2 and roughness was reduced to 0.622 μm. Thus, based on the results, it was anticipated that the development of degradable materials and implants would be feasible using this method. This study aims to fabricate MAO coatings for orthopedic magnesium implants that can enhance bioactivity, biocompatibility, and prevent additional surgery and implant-related infections to be used in clinical applications.

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

1985 ◽  
Vol 108 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Thyroid Hormone ◽  
Dose Level ◽  
Hormone Secretion ◽  
High Dose ◽  
Inhibitory Effects ◽  
High Dose Level ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

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