scholarly journals Bone Morphology is Regulated Modularly by Global and Regional Genetic Programs

2018 ◽  
Author(s):  
Shai Eyal ◽  
Shiri Kult ◽  
Sarah Rubin ◽  
Sharon Krief ◽  
Kyriel M. Pineault ◽  
...  
Keyword(s):  
Bone Development ◽  
Genetic Regulation ◽  
Light Sheet ◽  
Long Bone ◽  
Genetic Lineage ◽  
Long Bones ◽  
Regulatory Modules ◽  
Different Shapes ◽  
Dose Dependent ◽  
Pattern Regulation

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.

scholarly journals New light shed on the early evolution of limb-bone growth plate and bone marrow

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jordi Estefa ◽  
Paul Tafforeau ◽  
Alice M Clement ◽  
Jozef Klembara ◽  
Grzegorz Niedźwiedzki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Bone Growth ◽  
Bone Development ◽  
Three Dimensional ◽  
Early Evolution ◽  
Long Bone ◽  
Long Bones ◽  
Limb Bone ◽  
Limb Bones

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.

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
Keyword(s):  
Trabecular Bone ◽  
Bone Tissue ◽  
Bone Development ◽  
Bone Mineralization ◽  
Antagonistic Effect ◽  
Hair Follicles ◽  
Long Bone ◽  
Long Bones ◽  
Epiphyseal Growth Plate ◽  
Alizarin Red

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.

scholarly journals The influence of a high-protein, low-carbohydrate diet on bone development in the fetuses of rat dams with streptozotocin-induced diabetes

1988 ◽  
Vol 59 (1) ◽  
pp. 57-62 ◽  
Author(s):  
W. Keith Harvey ◽  
Tetsuo Nakamoto
Keyword(s):  
G Protein ◽  
Collagen Synthesis ◽  
Bone Development ◽  
High Protein ◽  
Diabetic Group ◽  
Long Bones ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Ca Uptake

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.

scholarly journals Collagen heterogeneity within different growth regions of long bones of rachitic and nonrachitic chicks

1972 ◽  
Vol 127 (4) ◽  
pp. 715-720 ◽  
Author(s):  
Bryan P. Toole ◽  
Andrew H. Kang ◽  
Robert L. Trelstad ◽  
Jerome Gross
Keyword(s):  
Vitamin D ◽  
Amino Acid ◽  
Bone Matrix ◽  
Bone Collagen ◽  
Long Bone ◽  
Long Bones ◽  
Collagen Structure ◽  
Collagen Molecules ◽  
Relationship Of ◽  
Chain Type

The different anatomical regions involved in osteogenesis in the chick long bone have been examined for heterogeneities in collagen structure that might relate to the mechanism of ossification. Experimentally induced lathyrism was employed to enhance collagen solubility, and vitamin D deficiency to allow accumulation of osteoid, the precursor of bone matrix. The extractable lathyritic collagens of the cartilaginous and osseous regions of growing long bones from rachitic and non-rachitic chicks were examined for α-chain type and amino acid composition. In both groups of animals the growth plate and cartilaginous regions of the epiphysis gave collagen molecules of the constitution [α1(II)]3, whereas the ossifying regions contained [α1(I)]2 α2. The degree of hydroxylation of the lysine moieties was increased by approximately 50% in the α1(I)-chain and α2-chain of rachitic bone collagen. Since uncalcified osteoid is greatly enriched in rachitic bone, it is concluded that the collagen of osteoid has the configuration [α1(I)]2 α2, similar to that of bone matrix, but has an elevated hydroxylysine content. The possible relationship of this difference to the mechanism of calcification is discussed.

Isolation, Culture and Identification of Bovine Skeletal Stem Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 2337-2345
Author(s):  
Junhui Lai ◽  
Qin Yang ◽  
Ruining Liang ◽  
Weijun Guan ◽  
Xiuxia Li
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Bone Formation ◽  
Growth Plate ◽  
Bone Development ◽  
Long Bone ◽  
Biological Characterization ◽  
Self Renewal ◽  
And Cartilage

The growth plate is essential in long bone formation and contains a wealth of skeletal stem cells (SSCs). Though the origin and the mechanism for SSCs generation remain uncertain, recent studies demonstrate the transition from cartilage to bone that in the lineage for bone development. SSCs possesses the ability to differentiate into bone and cartilage in vitro. In this research, we aimed to isolate and culture the skeletal stem cells from bovine cattle and then studied its biological characterization. The results showed that these bovine SSCs are positive for PDPN+CD73+CD164+CD90+CD44+ cell surface bio-markers, they are capable of self-renewal and differentiation. Our dates proved that SSCs exists in bovine’s long bone.

Long-bone development and life-history traits of the Devonian tristichopterid Hyneria lindae

2018 ◽  
Vol 109 (1-2) ◽  
pp. 75-86 ◽  
Author(s):  
Viktoriia KAMSKA ◽  
Edward B. DAESCHLER ◽  
Jason P. DOWNS ◽  
Per E. AHLBERG ◽  
Paul TAFFOREAU ◽  
...  
Keyword(s):  
Life History ◽  
Limb Development ◽  
Life History Traits ◽  
Bone Development ◽  
Bone Histology ◽  
Long Bone ◽  
General Character ◽  
Appendicular Skeleton ◽  
Predatory Behaviour ◽  
Large Size

ABSTRACTHyneria lindae is one of the largest Devonian sarcopterygians. It was found in the Catskill Formation (late Famennian) of Pennsylvania, USA. The current study focuses on the palaeohistology of the humerus of this tristichopterid and supports a low ossification rate and a late ossification onset in the appendicular skeleton. In addition to anatomical features, the large size of the cell lacunae in the cortical bone of the humerus mid-shaft may suggest a large genome size and associated neotenic condition for this species, which could, in turn, be a partial explanation for the large size of H. lindae. The low metabolism of H. lindae revealed here by bone histology supports the hypothesis of an ambush predatory behaviour. Finally, the lines-of-arrested-growth pattern and late ossification of specimen ANSP 21483 suggest that H. lindae probably had a long juvenile stage before reaching sexual maturity. Although very few studies address the life-history traits of stem tetrapods, they all propose a slow limb development for the studied taxa despite different ecological conditions and presumably distinct behaviours. The bone histology of H. lindae would favour the hypothesis that a slow long-bone development could be a general character for stem tetrapods.

Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Growth ◽  
Long Bone ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Serum Free ◽  
Factor I ◽  
Igf I

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.

scholarly journals Exposure to the RXR agonist SR11237 in early life causes disturbed skeletal morphogenesis in a rat model

2019 ◽  
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Long Bone ◽  
Tunel Staining ◽  
Long Bones ◽  
Micro Computed Tomography ◽  
Computed Tomography Scanning ◽  
Calcified Tissue ◽  
Trap Staining ◽  
Tomography Scanning

AbstractLongitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation on EO.Rats given SR11237 from post-natal day 5 to 15 were harvested for micro-computed tomography scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole mount evaluation.RXR agonist-treated rats were smaller than controls, and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape corresponding with P57 immunostaining. Additionally, SOX9 positive cells were found surrounding the calcified tissue. The epiphysis of SR11237 treated bones showed increased TRAP staining, and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of treated animals. Isolated mouse long bones treated with SR11237 grew significantly less than their DMSO controls.This study demonstrates that stimulation of the RXR receptor causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models.

scholarly journals The first report of direct skeletal attachment method applying for tibia prosthetic leg in a chicken by cortical screw

2019 ◽  
Vol 2 (3) ◽  
pp. 3-5
Author(s):  
Piyabongkarn Damrongdej
Keyword(s):  
Stainless Steel ◽  
Blood Loss ◽  
Endotracheal Tube ◽  
Surgical Procedure ◽  
Small Animal ◽  
Long Bone ◽  
Long Bones ◽  
First Report ◽  
Cortical Screw ◽  
Intramedullary Screw

This is the first report of successful method for direct skeletal attachment for invent tibia prosthetic leg in a chicken amputee by using 3.0 mm stainless steel cortical screw as an intramedullary bone stem for right tibia endoprosthesis leg part and using acrylic with some part of endotracheal tube as an exoprosthesis leg part. This surgery was performed in a chicken amputee without bone cement using. A chicken could stand and sometime walk after 15 days of surgery. No complication problem with a screw’s stump. This intramedullary bone stem technique by a screw can adapt using in other parts of long bone animal amputee. This technique can apply for invent endoprosthesis limb in other small animal amputees and can use intramedullary screw technique with other long bones such as femur, humerus, radius, and ulna because this technique uses only one stainless 316L screw so the surgery cost is not too much. The surgical procedure is not complicated and blood loss during surgery is not much so the risk for this technique is low.

scholarly journals Rac signaling in osteoblastic cells is required for normal bone development but is dispensable for hematopoietic development

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 736-744 ◽  
Author(s):  
Steven W. Lane ◽  
Serena De Vita ◽  
Kylie A. Alexander ◽  
Ruchan Karaman ◽  
Michael D. Milsom ◽  
...  
Keyword(s):  
Bone Growth ◽  
Bone Development ◽  
Long Bone ◽  
Perivascular Niche ◽  
Hematopoietic Stem ◽  
Hsc Niche ◽  
Rac1 Gtpase

Abstract Hematopoietic stem cells (HSCs) interact with osteoblastic, stromal, and vascular components of the BM hematopoietic microenvironment (HM) that are required for the maintenance of long-term self-renewal in vivo. Osteoblasts have been reported to be a critical cell type making up the HSC niche in vivo. Rac1 GTPase has been implicated in adhesion, spreading, and differentiation of osteoblast cell lines and is critical for HSC engraftment and retention. Recent data suggest a differential role of GTPases in endosteal/osteoblastic versus perivascular niche function. However, whether Rac signaling pathways are also necessary in the cell-extrinsic control of HSC function within the HM has not been examined. In the present study, genetic and inducible models of Rac deletion were used to demonstrate that Rac depletion causes impaired proliferation and induction of apoptosis in the OP9 cell line and in primary BM stromal cells. Deletion of Rac proteins caused reduced trabecular and cortical long bone growth in vivo. Surprisingly, HSC function and maintenance of hematopoiesis in vivo was preserved despite these substantial cell-extrinsic changes. These data have implications for therapeutic strategies to target Rac signaling in HSC mobilization and in the treatment of leukemia and provide clarification to our evolving concepts of HSC-HM interactions.

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