scholarly journals Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.

1996 ◽  
Vol 132 (1) ◽  
pp. 195-210 ◽  
Author(s):  
A Erlebacher ◽  
R Derynck
Keyword(s):  
Bone Cells ◽  
Bone Development ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Cell Types ◽  
Cleidocranial Dysplasia ◽  
Tgf Beta ◽  
Matrix Deposition ◽  
Beta 2 ◽  
High Level

The development of the skeleton requires the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The activities of these two cell types are likely to be regulated by TGF-beta, which is abundant in bone matrix. We have used transgenic mice to evaluate the role of TGF-beta 2 in bone development and turnover. Osteoblast-specific overexpression of TGF-beta 2 from the osteocalcin promoter resulted in progressive bone loss associated with increases in osteoblastic matrix deposition and osteoclastic bone resorption. This phenotype closely resembles the bone abnormalities seen in human hyperparathyroidism and osteoporosis. Furthermore, a high level of TGF-beta 2 overexpression resulted in defective bone mineralization and severe hypoplasia of the clavicles, a hallmark of the developmental disease cleidocranial dysplasia. Our results suggest that TGF-beta 2 functions as a local positive regulator of bone remodeling and that alterations in TGF-beta 2 synthesis by bone cells, or in their responsiveness to TGF-beta 2, may contribute to the pathogenesis of metabolic bone disease.

scholarly journals Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

2020 ◽  
Vol 21 (16) ◽  
pp. 5600 ◽  
Author(s):  
Jean Vacher ◽  
Michael Bruccoleri ◽  
Monica Pata
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Fractures ◽  
Bone Development ◽  
Bone Matrix ◽  
Adult Life ◽  
Cell Types ◽  
Severe Form ◽  
Isolation And Characterization

The maintenance of bone mass is a dynamic process that requires a strict balance between bone formation and resorption. Bone formation is controlled by osteoblasts, while osteoclasts are responsible for resorption of the bone matrix. The opposite functions of these cell types have to be tightly regulated not only during normal bone development, but also during adult life, to maintain serum calcium homeostasis and sustain bone integrity to prevent bone fractures. Disruption of the control of bone synthesis or resorption can lead to an over accumulation of bone tissue in osteopetrosis or conversely to a net depletion of the bone mass in osteoporosis. Moreover, high levels of bone resorption with focal bone formation can cause Paget’s disease. Here, we summarize the steps toward isolation and characterization of the osteopetrosis associated trans-membrane protein 1 (Ostm1) gene and protein, essential for proper osteoclast maturation, and responsible when mutated for the most severe form of osteopetrosis in mice and humans.

scholarly journals Accumulation, localization, and compartmentation of transforming growth factor beta during endochondral bone development.

1988 ◽  
Vol 107 (5) ◽  
pp. 1969-1975 ◽  
Author(s):  
J L Carrington ◽  
A B Roberts ◽  
K C Flanders ◽  
N S Roche ◽  
A H Reddi
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bone Development ◽  
Guanidine Hydrochloride ◽  
Bone Matrix ◽  
Radioreceptor Assay ◽  
Tgf Beta ◽  
Endochondral Bone ◽  
Growth Factor Beta

Endochondral bone formation was induced in postnatal rats by implantation of demineralized rat bone matrix. Corresponding control tissue was generated by implanting inactive extracted bone matrix, which did not induce bone formation. At various times, implants were removed and sequentially extracted with guanidine hydrochloride, and then EDTA and guanidine hydrochloride. Transforming growth factor beta (TGF beta) in the extracts was quantitated by a radioreceptor assay. TGF beta was present in demineralized bone matrix before implantation, and the concentration had decreased by 1 d after implantation. Thereafter, TGF beta was undetectable by radioreceptor assay until day 9. From day 9-21 the TGF beta was extracted only after EDTA demineralization, indicating tight association with the mineralized matrix. During this time, the content of TGF beta per milligram soluble protein rose steadily and remained high through day 21. This increased concentration correlated with the onset of vascularization and calcification of cartilage. TGF beta was detected only between days 3-9 in the controls; i.e., non-bone-forming implants. Immunolocalization of TGF beta in bone-forming implants revealed staining of inflammatory cells at early times, followed later by staining of chondrocytes in calcifying cartilage and staining of osteoblasts. The most intense staining of TGF beta was found in calcified cartilage and mineralized bone matrix, again indicating preferential compartmentalization of TGF beta in the mineral phase. In contrast to the delayed expression of TGF beta protein, northern blot analysis showed TGF beta mRNA in implants throughout the sequence of bone formation. The time-dependent accumulation of TGF beta when cartilage is being replaced by bone in this in vivo model of bone formation suggests that TGF beta may play a role in the regulation of ossification during endochondral bone development.

scholarly journals Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 195-200 ◽  
Author(s):  
Cecilia H. A. Gouveia ◽  
Marcelo A. Christoffolete ◽  
Clarissa R. Zaitune ◽  
José Miguel Dora ◽  
John W. Harney ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cell Line ◽  
Bone Cells ◽  
Bone Development ◽  
Cell Types ◽  
Osteoblastic Cell ◽  
Dependent Manner ◽  
Osteoblastic Cell Line ◽  
Serum T3

Thyroid hormone affects multiple aspects of bone metabolism, but little is known about thyroid hormone deiodination in bone cells except that cultures of skeletal cells and bone organ express types 1 and 2 iodothyronine deiodinases (D1 and D2) mRNAs. In the present study, outer ring deiodination (ORD) activity was detected in bone extracts of multiple sites of the mouse skeleton, bone marrow, and the MC3T3-E1 osteoblastic cell line. In all tissues, ORD was detected using 125I-rT3 or 125I-T4 as substrates and was found to be 6-n-propylthiouracil insensitive, display a Michaelis constant (T4) of approximately 1 nm, increase about 3-fold in hypo- and virtually disappear in thyrotoxicosis. Extracts of calvaria had the lowest ORD activity, whereas tibial and femoral extracts had roughly three times as much. The absence of ORD activity in bone extracts from mice with targeted disruption of the Dio2 gene confirms the principal role of D2 in this tissue. In the MC3T3-E1 osteoblasts, D2 activity increased in a time-dependent manner after plating, and with the content of selenium in the media, reaching a maximum 5–7 d later as cells attained more than 90% confluence. In these cells D2 half-life is about 30–40 min, which is further accelerated by exposure to substrate and stabilized by the proteasome inhibitor, MG132. Treatment with vitamin D [1,25(OH)2VD]-induced D2 activity by 2- to 3-fold as early as 24 h, regardless of the level of cell confluence, but estradiol, PTH, forskolin, leptin, TNFα, TGFβ, and dexamethasone did not affect D2. Given the role of D2 in other cell types and processes, it is likely that bone ORD not only plays a role in bone development and adult bone T3 homeostasis but also contributes to extrathyroidal T3 production and maintenance of serum T3.

scholarly journals Transforming growth factor-beta 1, -beta 2 and -beta 3 in cartilage and bone cells during endochondral ossification in the chick

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 907-911 ◽  
Author(s):  
B.H. Thorp ◽  
I. Anderson ◽  
S.B. Jakowlew
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Type Ii Collagen ◽  
Hypertrophic Chondrocytes ◽  
Nuclear Staining ◽  
Tgf Beta ◽  
Specific Localization ◽  
Growth Factor Beta ◽  
Beta 2

The localization of TGF-beta 1, -beta 2 and -beta 3 was studied in the growth plate, epiphysis and metaphysis of the tibiotarsus of three-week-old chicks. The different TGF-beta isoforms were localized to hypertrophic chondrocytes, chondroclasts, osteoblasts and osteoclasts using immunohistochemical staining analysis with specific TGF-beta antibodies. TGF-betas in osteoclasts and chondroclasts were restricted to those cells located on the respective matrices. TGF-beta 3 localization was mainly cytoplasmic in the transitional (early hypertrophic) chondrocytes, but nuclear staining was also detected in some proliferating chondrocytes. The cell-specific localization of these TGF-beta isoforms supports the hypothesis that TGF-beta has a role in the coupling of new bone formation to bone and cartilage matrix resorption during osteochondral development and suggests that TGF-beta may be a marker of chondrocyte differentiation. TGF-beta localization preceded a marked increase in type II collagen mRNA expression in transitional chondrocytes, suggesting a role for TGF-beta in the induction of synthesis of extracellular matrix.

scholarly journals Bone sialoprotein (BSP) secretion and osteoblast differentiation: relationship to bromodeoxyuridine incorporation, alkaline phosphatase, and matrix deposition.

1993 ◽  
Vol 41 (2) ◽  
pp. 183-191 ◽  
Author(s):  
P Bianco ◽  
M Riminucci ◽  
E Bonucci ◽  
J D Termine ◽  
P G Robey
Keyword(s):  
Bone Formation ◽  
Bone Cells ◽  
Cell Types ◽  
Brdu Incorporation ◽  
Functional Equivalence ◽  
Matrix Deposition ◽  
Osteogenic Cells ◽  
Cell Compartments ◽  
Bone Deposition

We defined two distinct maturational compartments (proliferative and secretory) of osteogenic cells in vivo on the basis of ALP activity, BrdU incorporation, cell shape, and BSP production. BSP immunoreactivity was found to mark cells in the secretory but not in the proliferative compartment. We established the phenotypic similarity of primitive marrow stromal cells with proliferating perichondral cells (fibroblast-like, ALP+, BrdU+, BSP-). This suggests the potential functional equivalence of the two cell types as committed non-secretory osteogenic cells and points to the duality of osteogenic cell compartments as a generalized feature of bone formation. We further showed that although BSP secretion is a hallmark of the onset of osteogenesis, BSP antigenicity is lost both in osteoid and in a large proportion of mature osteoblasts during subsequent phases of bone deposition. This suggests that bone formation may not be a uniform event, as bone cells actually deposit antigenically, and likely biochemically, distinct matrices at specific times.

scholarly journals Role of Metabolism in Bone Development and Homeostasis

2020 ◽  
Vol 21 (23) ◽  
pp. 8992
Author(s):  
Akiko Suzuki ◽  
Mina Minamide ◽  
Chihiro Iwaya ◽  
Kenichi Ogata ◽  
Junichi Iwata
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Bone Cells ◽  
Bone Development ◽  
Bone Matrix ◽  
The Body ◽  
Cellular Functions ◽  
Genetic Studies ◽  
Cellular Dysfunction

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.

Tissue-specific expression of bone proteins in femora of growing rats

1992 ◽  
Vol 263 (4) ◽  
pp. E724-E729 ◽  
Author(s):  
R. T. Turner ◽  
S. N. Kapelner ◽  
T. C. Spelsberg
Keyword(s):  
Bone Formation ◽  
Type I Collagen ◽  
Bone Cells ◽  
Bone Matrix ◽  
Type I ◽  
Mrna Levels ◽  
Specific Expression ◽  
Matrix Deposition ◽  
Periosteal Cells ◽  
Old Rats

Total cellular RNA was extracted from bone cells of three different femoral compartments of 2-mo-old rats. The intact femora were first incubated with collagenase to obtain periosteal cells. The bisected periosteum-free diaphyses and metaphyses were then incubated with collagenase to obtain enriched populations of endosteal and cancellous bone cells, respectively. The total cellular RNA from these three tissues was separated by size using agarose gel electrophoresis, transferred to nylon filters, hybridized to 32P-labeled cDNA probes for glyceraldehyde-3-phosphate dehydrogenase (GAP), pre-pro-alpha (I) type I collagen (collagen), osteocalcin (BGP), and alkaline phosphatase (AP), and the cDNA/mRNA hybrids were visualized by radioautography. Bone matrix deposition was measured in each tissue compartment by tetracycline-based dynamic bone histomorphometry. The bone formation and apposition rates were greatest in the periosteum and least in metaphysis. Mean mRNA levels for collagen and BGP were positively correlated with mean bone formation and mineral apposition rates. Interestingly, mean AP mRNA levels were not correlated with indexes of bone formation. These results demonstrate that the steady-state mRNA levels for bone matrix proteins in femora show pronounced site specificity and correlate with the rates of bone matrix deposition.

scholarly journals The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7253
Author(s):  
Georgiana Neag ◽  
Melissa Finlay ◽  
Amy J. Naylor
Keyword(s):  
Endothelial Cells ◽  
Bone Formation ◽  
Drug Targets ◽  
Bone Development ◽  
Cell Types ◽  
Regulatory Relationship ◽  
Sequencing Technologies ◽  
Resolution Imaging ◽  
Molecular Relationships ◽  
Form Type

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.

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