scholarly journals BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

2022 ◽  
Vol 23 (2) ◽  
pp. 785
Author(s):  
Ivan Banovac ◽  
Lovorka Grgurevic ◽  
Viktorija Rumenovic ◽  
Slobodan Vukicevic ◽  
Igor Erjavec

Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female Bmp3−/− mice. To investigate the effect of Bmp3 from birth to maturity, we compared Bmp3−/− mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age. Bmp3 deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The Bmp3 reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of Bmp3−/− mice. Bmp3 deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult Bmp3−/− mice.

TRAUMA ◽  
2021 ◽  
Vol 22 (4) ◽  
pp. 37-45
Author(s):  
O.E. Vyrva ◽  
Ya.О. Golovina ◽  
R.V. Malik ◽  
M.Yu. Karpinsky ◽  
О.V. Yaresko

Background. Replacement of post-resection defects of long bones in case of a tumor process is always an urgent problem of orthopedics. Among the wide variety of materials and methods for reconstruction of post-resection defects of long bones, the most common are individual, modular arthroplasty and bioreconstructive interventions. To study the mechanical properties of the structures we have chosen, various types of post-resection femoral bone defect replacement were simulated using the finite element method. The purpose was to compare the data on stress-strain states in mathematical models “allocomposite endoprosthesis” and “individual endoprosthesis” of the proximal femur. Material and methods. Mathematical models of the femur with the formation of a post-resection proximal defect replaced by a segmental bone allograft in combination with an individual endoprosthesis have been created. The model is presented in two versions, with the formation of transverse and step-cut osteotomy. Each model was examined separately with cement and cementless attachment in the area of the endoprosthesis stem. For comparison, we chose a model with complete replacement of the proximal end of the femur with an individual endoprosthesis without bone grafting. Results. Femur step-cut osteotomy can significantly reduce the level of stress in the osteotomy area. This is due to the fact that performing the step-cut osteotomy allows the bone fragments to provide resistance to shearing movement. The use of bone cement can significantly reduce the level of stress around the stem of the endoprosthesis in both variants of femoral osteotomy (transverse and step-cut). This is due to the fact that bone cement, which has an elastic modulus at an intermediate value between titanium and bone tissue, forms a layer between them, performs a damper function, that smoothes the difference in deformation values of the metal and bone tissue, thereby reducing the level of stress in them. Arthroplasty without performing bone grafting leads to increased stresses in the bone tissue due to the presence of a rigid support on the cortical bone endoprosthesis in the diaphysis along the line of its resection. Conclusions. Performing step-cut osteotomy of the femur reduces the level of mechanical stresses in the osteotomy area by half compared to models with transverse osteotomy, which is of particular importance in the early postoperative stages. The use of bone cement for fixing the stem of the endoprosthesis can also significantly reduce the level of stress in all variants of the studied models, due to the formation of a damping layer between the metal and the bone tissue. The level of stress in models without bone grafting does not depend on the use of bone cement, but is determined by the presence of a rigid support of the endoprosthesis on the cortical bone along the line of its resection.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jordi Estefa ◽  
Paul Tafforeau ◽  
Alice M Clement ◽  
Jozef Klembara ◽  
Grzegorz Niedźwiedzki ◽  
...  

The production of blood cells (haematopoiesis) occurs in the limb bones of most tetrapods but is absent in the fin bones of ray-finned fish. When did long bones start producing blood cells? Recent hypotheses suggested that haematopoiesis migrated into long bones prior to the water-to-land transition and protected newly-produced blood cells from harsher environmental conditions. However, little fossil evidence to support these hypotheses has been provided so far. Observations of the humeral microarchitecture of stem-tetrapods, batrachians, and amniotes were performed using classical sectioning and three-dimensional synchrotron virtual histology. They show that Permian tetrapods seem to be among the first to exhibit a centralised marrow organisation, which allows haematopoiesis as in extant amniotes. Not only does our study demonstrate that long-bone haematopoiesis was probably not an exaptation to the water-to-land transition but it sheds light on the early evolution of limb-bone development and the sequence of bone-marrow functional acquisitions.


2019 ◽  
Vol 20 (12) ◽  
pp. 2872 ◽  
Author(s):  
Agnieszka Strzelecka-Kiliszek ◽  
Marta Romiszewska ◽  
Lukasz Bozycki ◽  
Saida Mebarek ◽  
Joanna Bandorowicz-Pikula ◽  
...  

Osteoblasts initiate bone mineralization by releasing matrix vesicles (MVs) into the extracellular matrix (ECM). MVs promote the nucleation process of apatite formation from Ca2+ and Pi in their lumen and bud from the microvilli of osteoblasts during bone development. Tissue non-specific alkaline phosphatase (TNAP) as well as annexins (among them, AnxA6) are abundant proteins in MVs that are engaged in mineralization. In addition, sarcoma proto-oncogene tyrosine-protein (Src) kinase and Rho-associated coiled-coil (ROCK) kinases, which are involved in vesicular transport, may also regulate the mineralization process. Upon stimulation in osteogenic medium containing 50 μg/mL of ascorbic acid (AA) and 7.5 mM of β-glycerophosphate (β-GP), human osteosarcoma Saos-2 cells initiated mineralization, as evidenced by Alizarin Red-S (AR-S) staining, TNAP activity, and the partial translocation of AnxA6 from cytoplasm to the plasma membrane. The addition of 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d] pyrimidine (PP2), which is an inhibitor of Src kinase, significantly inhibited the mineralization process when evaluated by the above criteria. In contrast, the addition of (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide hydrochloride (Y-27632), which is an inhibitor of ROCK kinase, did not affect significantly the mineralization induced in stimulated Saos-2 cells as denoted by AR-S and TNAP activity. In conclusion, mineralization by human osteosarcoma Saos-2 cells seems to be differently regulated by Src and ROCK kinases.


Author(s):  
V.M. Shуmon ◽  
S.P. Alfeldii ◽  
M.V. Shуmon ◽  
V.V. Stoіka

One of the most promising trends in contemporary traumatology and orthopaedics towards the treatment of fractures and bone defects is the use of synthetic calcium-phosphate biomaterials. The purpose of this study is to identify the features of bone defect healing in rats during the implantation of calcium phosphate glass crystalline materials, and to substantiate the feasibility of the use of bioglass in the clinical treatment of fractures and defects of long bones. Materials and methods. In this study we used bioactive calcium-phosphate glass crystal material BS-11. The experimental part was performed on 36 white rats. The animals were subjected to defect modelling in the femur with following bioglass filling. Results. We observed the formation of osteogenic fibroreticular tissue and bone tissue of varying degrees of maturity around the implanted filling samples through all the healing periods. The relative content of bone tissue in the surrounding regenerated tissue around the studied samples BS-11 increased in parallel with the increase of the observation period and reached 100% in 30 days after the surgical operation and at the end of the study we registered the formation of bone tissue of the lamellar structure around the samples inserted. We observed no signs of inflammation or any cellular reaction in any of the cases studies that points out the biocompatibility of the material. Conclusions. Morphological study has demonstrated that the insertion of cylindrical blocks made of glass-crystalline calcium phosphate materials BC-11 in the distal metaphysis of the femur of rats and healing is accompanied with osteoregeneration around them in accordance with the conventional stages of the bone tissue formation. This material can be recommended for treating long bone defects of different aetiology.


2018 ◽  
Author(s):  
Shai Eyal ◽  
Shiri Kult ◽  
Sarah Rubin ◽  
Sharon Krief ◽  
Kyriel M. Pineault ◽  
...  

ABSTRACTDuring skeletogenesis, a variety of protrusions of different shapes and sizes develop on the surfaces of long bones. These superstructures provide stable anchoring sites for ligaments and tendons during the assembly of the musculoskeletal system. Despite their importance, the mechanism by which superstructures are patterned and ultimately give rise to the unique morphology of each long bone is far from understood. In this work, we provide further evidence that long bones form modularly from Sox9+ cells, which contribute to their substructure, and from Sox9+/Scx+ progenitors that give rise to superstructures. Moreover, we identify components of the genetic program that controls the patterning of Sox9+/Scx+ progenitors and show that this program includes both global and regional regulatory modules.Using light sheet fluorescence microscopy combined with genetic lineage labeling, we mapped the broad contribution of the Sox9+/Scx+ progenitors to the formation of bone superstructures. Additionally, by combining literature-based evidence and comparative transcriptomic analysis of different Sox9+/Scx+ progenitor populations, we identified genes potentially involved in patterning of bone superstructures. We present evidence indicating that Gli3 is a global regulator of superstructure patterning, whereas Pbx1, Pbx2, Hoxa11 and Hoxd11 act as proximal and distal regulators, respectively. Moreover, by demonstrating a dose-dependent pattern regulation in Gli3 and Pbx1 compound mutations, we show that the global and regional regulatory modules work coordinately. Collectively, our results provide strong evidence for genetic regulation of superstructure patterning that further supports the notion that long bone development is a modular process.


Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1051
Author(s):  
Gennady Kolesnikov ◽  
Rudolf Meltser

Experimental research of bone strength remains costly and limited for ethical and technical reasons. Therefore, to predict the mechanical state of bone tissue, as well as similar materials, it is desirable to use computer technology and mathematical modeling. Yet, bone tissue as a bio-mechanical object with a hierarchical structure is difficult to analyze for strength and rigidity; therefore, empirical models are often used, the disadvantage of which is their limited application scope. The use of new analytical solutions overcomes the limitations of empirical models and significantly improves the way engineering problems are solved. Aim of the paper: the development of analytical solutions for computer models of the mechanical state of bone and similar materials. Object of research: a model of trabecular bone tissue as a quasi-brittle material under uniaxial compression (or tension). The new ideas of the fracture mechanics, as well as the methods of mathematical modeling and the biomechanics of bone tissues were used in the work. Compression and tension are considered as asymmetric mechanical states of the material. Results: a new nonlinear function that simulates both tension and compression is justified, analytical solutions for determining the effective and apparent elastic modulus are developed, the residual resource function and the damage function are justified, and the dependences of the initial and effective stresses on strain are obtained. Using the energy criterion, it is proven that the effective stress continuously increases both before and after the extremum point on the load-displacement plot. It is noted that the destruction of bone material is more likely at the inflection point of the load-displacement curve. The model adequacy is explained by the use of the energy criterion of material degradation. The results are consistent with the experimental data available in the literature.


2016 ◽  
Vol 195 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Michael Kerschnitzki ◽  
Anat Akiva ◽  
Adi Ben Shoham ◽  
Yotam Asscher ◽  
Wolfgang Wagermaier ◽  
...  

1988 ◽  
Vol 59 (1) ◽  
pp. 57-62 ◽  
Author(s):  
W. Keith Harvey ◽  
Tetsuo Nakamoto

1. The purpose of the present study was to determine the effects of diet on the mandibles and growth centres of the long bones in the fetuses of diabetic rat dams given a normal diet compared with those given a high-protein, low-carbohydrate diet.2. On the 9th day of gestation, the controls, groups 1 and 3, were injected with citrate buffer and given 200 and 600 g protein/kg diets respectively. Groups 2 and 4 were injected with 40 mg streptozotocin/kg body-weight and pair-fed with groups I and 3 respectively on the 200 and 600 g protein/kg diets.3. On day 22, some dams were injected with either 45Ca or [14C]proline. Mandibles and long bones were removed and weighed and analysed for Ca content, 45Ca uptake, collagen and collagen synthesis.4. The body-weights, and mandibular and long-bone weights of the fetuses in the diabetic 200 g protein/kg group were smaller than those of the non-diabetic 200 g protein/kg group, whereas those of the diabetic 600 g protein/kg group showed no difference from the non-diabetic 600 g protein/kg group.5. The rate of collagen synthesis was higher in the fetuses of the diabetic 600 g protein/kg group than those of the non-diabetic group. Bones of the diabetic 200 g protein/kg group were lower in collagen content when compared with the non-diabetic group, whereas there was no difference between the diabetic and non-diabetic 600 g protein/kg groups.6. Ca uptake and total Ca contents in the mandibles and long bones showed no difference between diabetic and non-diabetic groups fed on both diets.7. A high-protein, low-carbohydrate diet appeared to have a certain beneficial effect on bone development of the growing fetuses from diabetic dams.


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