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.

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 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.

scholarly journals Quantification and three-dimensional microanatomical organization of the bone marrow

2017 ◽  
Vol 1 (6) ◽  
pp. 407-416 ◽  
Author(s):  
Cesar Nombela-Arrieta ◽  
Markus G. Manz
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Structural Organization ◽  
Imaging Techniques ◽  
White Blood Cells ◽  
Three Dimensional ◽  
The Body ◽  
Cellular Composition ◽  
Spatial Logic ◽  
Health And Disease

Abstract Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease.

scholarly journals Feasibility of three-dimensional reconstruction and automated measurement of fetal long bones using 5D Long Bone

2015 ◽  
Vol 58 (4) ◽  
pp. 268 ◽  
Author(s):  
Hyewon Hur ◽  
Young Han Kim ◽  
Hee Young Cho ◽  
Yong Won Park ◽  
Hye-Sung Won ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Long Bone ◽  
Long Bones ◽  
Automated Measurement ◽  
Three Dimensional Reconstruction ◽  
Dimensional Reconstruction

Heterogeneous Versus Homogeneous Material Considerations in Determining the Modal Frequencies of Long Tibia Bones

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Reem A. Yassine ◽  
Mohammad Karim Elham ◽  
Samir Mustapha ◽  
Ramsey F. Hamade
Keyword(s):  
Three Dimensional ◽  
Heterogeneous Material ◽  
Approximate Solutions ◽  
3D Models ◽  
Long Bone ◽  
Homogeneous Material ◽  
Long Bones ◽  
Bone Properties ◽  
Mode 2 ◽  
Experimental Values

Where heterogeneous material considerations may yield more accurate estimates of long bones' modal characteristics, homogeneous description yields faster approximate solutions. Here, modal frequencies of (bovine) long tibia bones are numerically estimated using the finite element method (FEM) (ANSYS) starting from anatomically accurate computed tomography (CT) scans. Whole long bones are segmented into cortical and cancellous constituents based on Hounsfield (HU) values. Accurate three-dimensional (3D) models are consequently developed. Bones' cortical and cancellous constituents are first treated as heterogeneous material. Relative to stiffness–density relations, stiffness values are assigned for each element yielding a stiffness-graded structure. Calculated modal frequencies are compared to those measured from dynamic experiments. Analysis was repeated where bone properties are homogenized by averaging the stiffness properties of bone constituents. Compared with experimental values of one control long bone, the heterogeneous material assumption returned good estimates of the frequency values in the cranial–caudal (CC) plane with of +0.85% for mode 1 and +10.66% for mode 2. For homogeneous material assumption, underestimates were returned with error values of −13.25% and −0.13% differences for mode 2. In the medial–lateral (ML) plane, heterogeneous material assumption returned good frequency estimates with −8.89% for mode 1 and +1.01% for mode 2. Homogeneous material assumption underestimated the frequency values with error of −20.52% for mode 1 and −7.50% for mode 2. Homogeneous simplifications yielded faster and more memory-efficient FEM runs with heterogeneous modal analysis requiring 1.5 more running time and twice the utilized memory.

scholarly journals The humerus of Eusthenopteron : a puzzling organization presaging the establishment of tetrapod limb bone marrow

2014 ◽  
Vol 281 (1782) ◽  
pp. 20140299 ◽  
Author(s):  
S. Sanchez ◽  
P. Tafforeau ◽  
P. E. Ahlberg
Keyword(s):  
Bone Marrow ◽  
Three Dimensional ◽  
Growth Patterns ◽  
Haematopoietic Stem Cell ◽  
Long Bone ◽  
Close Relationship ◽  
Dimensional Reconstruction ◽  
Bone Elongation ◽  
Synchrotron Microtomography ◽  
Stem Cell Niches

Because of its close relationship to tetrapods, Eusthenopteron is an important taxon for understanding the establishment of the tetrapod body plan. Notably, it is one of the earliest sarcopterygians in which the humerus of the pectoral fin skeleton is preserved. The microanatomical and histological organization of this humerus provides important data for understanding the evolutionary steps that built up the distinctive architecture of tetrapod limb bones. Previous histological studies showed that Eusthenopteron 's long-bone organization was established through typical tetrapod ossification modalities. Based on a three-dimensional reconstruction of the inner microstructure of Eusthenopteron 's humerus, obtained from propagation phase-contrast X-ray synchrotron microtomography, we are now able to show that, despite ossification mechanisms and growth patterns similar to those of tetrapods, it also retains plesiomorphic characters such as a large medullary cavity, partly resulting from the perichondral ossification around a large cartilaginous bud as in actinopterygians. It also exhibits a distinctive tubular organization of bone-marrow processes. The connection between these processes and epiphyseal structures highlights their close functional relationship, suggesting that either bone marrow played a crucial role in the long-bone elongation processes or that trabecular bone resulting from the erosion of hypertrophied cartilage created a microenvironment for haematopoietic stem cell niches.

scholarly journals Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model

2019 ◽  
Vol 20 (20) ◽  
pp. 5198
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Growth Plate ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Long Bone ◽  
Tunel Staining ◽  
Long Bones ◽  
Micro Computed Tomography ◽  
Calcified Tissue ◽  
Trap Staining ◽  
Stimulation Of

Longitudinal 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 in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) 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 had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence 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 the treated animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models

scholarly journals Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
James N. Fisher ◽  
Giuseppe M. Peretti ◽  
Celeste Scotti
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Bone Regeneration ◽  
Bone Growth ◽  
Long Bone ◽  
Advantages And Disadvantages ◽  
Naturally Occurring ◽  
Cell Sources ◽  
Alternative Techniques ◽  
Developmental Engineering

Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates.

The Differential Growth-response of Embryonic Chick Limb-bone Rudiments to Triiodothyronine in vitro

Development ◽  
1961 ◽  
Vol 9 (3) ◽  
pp. 534-555
Author(s):  
Kirstie Lawson
Keyword(s):  
Tissue Culture ◽  
Growth Response ◽  
Differential Response ◽  
Long Bone ◽  
Long Bones ◽  
Embryonic Chick ◽  
Differential Growth ◽  
Limb Bone ◽  
Stage Of Development

The maturation of the cartilage of embryonic chick long-bone rudiments growing in tissue culture is accelerated by addition of the thyroid hormones, thyroxine and triiodothyronine, but the growth in length of different long bones is not uniformly affected (Fell & Mellanby, 1955, 1956). Thus the growth of the hormone-treated tibia is less than that of a normal tibia, while the effect of thyroid hormone on the radius is to increase its growth. This differential response is not determined either by the stage of development at which the limb-bone rudiments are exposed to hormone, or by the size of the explant (Lawson, 1961). Investigations to determine whether the differential response of limb-bone rudiments to triiodothyronine (T3) is due to differences in the growth rates of different bones are described in this paper. The work was divided into three parts.

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