scholarly journals NF-κB activation impedes the transdifferentiation of hypertrophic chondrocytes at the growth plate of mouse embryos in diabetic pregnancy

2021 ◽  
Vol 31 ◽  
pp. 52-61
Author(s):  
Xi Liu ◽  
Fan Qian ◽  
Qiwei Fan ◽  
Li Lin ◽  
Meiyao He ◽  
...  
Keyword(s):  
Growth Plate ◽  
Mouse Embryos ◽  
Diabetic Pregnancy ◽  
Hypertrophic Chondrocytes

scholarly journals Conditional Deletion of Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Reveals Its Essential Role in Chondrocyte Function and Endochondral Bone Formation

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 127-140 ◽  
Author(s):  
Shaohong Cheng ◽  
Weirong Xing ◽  
Sheila Pourteymoor ◽  
Jan Schulte ◽  
Subburaman Mohan
Keyword(s):  
Bone Formation ◽  
Growth Plate ◽  
Prolyl Hydroxylase ◽  
Conditional Knockout ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Bone Surface ◽  
Endochondral Bone ◽  
Prolyl Hydroxylase Domain

Abstract The hypoxic growth plate cartilage requires hypoxia-inducible factor (HIF)-mediated pathways to maintain chondrocyte survival and differentiation. HIF proteins are tightly regulated by prolyl hydroxylase domain-containing protein 2 (Phd2)-mediated proteosomal degradation. We conditionally disrupted the Phd2 gene in chondrocytes by crossing Phd2 floxed mice with type 2 collagen-α1-Cre transgenic mice and found massive increases (>50%) in the trabecular bone mass of long bones and lumbar vertebra of the Phd2 conditional knockout (cKO) mice caused by significant increases in trabecular number and thickness and reductions in trabecular separation. Cortical thickness and tissue mineral density at the femoral middiaphysis of the cKO mice were also significantly increased. Dynamic histomorphometric analyses revealed increased longitudinal length and osteoid surface per bone surface in the primary spongiosa of the cKO mice, suggesting elevated conversion rate from hypertrophic chondrocytes to mineralized bone matrix as well as increased bone formation in the primary spongiosa. In the secondary spongiosa, bone formation measured by mineralizing surface per bone surface and mineral apposition rate were not changed, but resorption was slightly reduced. Increases in the mRNA levels of SRY (sex determining region Y)-box 9, osterix (Osx), type 2 collagen, aggrecan, alkaline phosphatase, bone sialoprotein, vascular endothelial growth factor, erythropoietin, and glycolytic enzymes in the growth plate of cKO mice were detected by quantitative RT-PCR. Immunohistochemistry revealed an increased HIF-1α protein level in the hypertrophic chondrocytes of cKO mice. Infection of chondrocytes isolated from Phd2 floxed mice with adenoviral Cre resulted in similar gene expression patterns as observed in the cKO growth plate chondrocytes. Our findings indicate that Phd2 suppresses endochondral bone formation, in part, via HIF-dependent mechanisms in mice.

scholarly journals Endoplasmic reticulum stress is induced in growth plate hypertrophic chondrocytes in G610C mouse model of osteogenesis imperfecta

2019 ◽  
Vol 509 (1) ◽  
pp. 235-240 ◽  
Author(s):  
Amanda L. Scheiber ◽  
Adam J. Guess ◽  
Takashi Kaito ◽  
Joshua M. Abzug ◽  
Motomi Enomoto-Iwamoto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Growth Plate ◽  
Hypertrophic Chondrocytes

Predominant expression of H3K9 methyltransferases in prehypertrophic and hypertrophic chondrocytes during mouse growth plate cartilage development

2013 ◽  
Vol 13 (3-4) ◽  
pp. 84-90 ◽  
Author(s):  
Hisashi Ideno ◽  
Akemi Shimada ◽  
Kazuhiko Imaizumi ◽  
Hiroshi Kimura ◽  
Masumi Abe ◽  
...  
Keyword(s):  
Growth Plate ◽  
Hypertrophic Chondrocytes ◽  
Growth Plate Cartilage ◽  
Cartilage Development ◽  
Predominant Expression

MORPHOLOGICAL AND BIOCHEMICAL EVIDENCE FOR APOPTOSIS IN THE TERMINAL HYPERTROPHIC CHONDROCYTES OF THE GROWTH PLATE

1996 ◽  
Vol 180 (4) ◽  
pp. 430-433 ◽  
Author(s):  
MICHIHISA ZENMYO ◽  
SETSURO KOMIYA ◽  
RIKIMARU KAWABATA ◽  
YASUYUKI SASAGURI ◽  
AKIO INOUE ◽  
...  
Keyword(s):  
Growth Plate ◽  
Hypertrophic Chondrocytes ◽  
Biochemical Evidence

scholarly journals SOXC Transcription Factors Induce Cartilage Growth Plate Formation in Mouse Embryos by Promoting Noncanonical WNT Signaling

2015 ◽  
Vol 30 (9) ◽  
pp. 1560-1571 ◽  
Author(s):  
Kenji Kato ◽  
Pallavi Bhattaram ◽  
Alfredo Penzo‐Méndez ◽  
Abhilash Gadi ◽  
Véronique Lefebvre
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Growth Plate ◽  
Mouse Embryos ◽  
Cartilage Growth ◽  
Plate Formation ◽  
Cartilage Growth Plate

scholarly journals Secondary ossification center induces and protects growth plate structure

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Meng Xie ◽  
Pavel Gol'din ◽  
Anna Nele Herdina ◽  
Jordi Estefa ◽  
Ekaterina V Medvedeva ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Growth Plate ◽  
Hypertrophic Chondrocytes ◽  
Ossification Center ◽  
Anatomical Entity ◽  
Terrestrial Environment ◽  
Force Microscopy ◽  
Atomic Force ◽  
High Mechanical Stress ◽  
Secondary Ossification Center

Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.

Hyaluronan contributes to the enlargement of hypertrophic lacunae in the growth plate

1996 ◽  
Vol 109 (2) ◽  
pp. 327-334 ◽  
Author(s):  
P. Pavasant ◽  
T. Shizari ◽  
C.B. Underhill
Keyword(s):  
Hydrostatic Pressure ◽  
Organ Culture ◽  
Growth Plate ◽  
Histochemical Staining ◽  
Culture Conditions ◽  
Hypertrophic Chondrocytes ◽  
Growth Plates ◽  
Normal Culture ◽  
Autoradiographic Analysis

Histochemical staining of the epiphysial growth plate revealed that free hyaluronan (i.e. available to the staining probe) was restricted to the zone of hypertrophy, where it was located in the pericellular space between the chondrocytes and the edge of the lacunae. Furthermore, the amount of hyaluronan staining was directly proportional to the size of the lacunae. Autoradiographic analysis of growth plates cultured with isotopically labeled glucosamine indicated that at least a portion of this hyaluronan was newly synthesized by the hypertrophic chondrocytes. Since hyaluronan can adsorb large amounts of water, it is possible that it exerted a hydrostatic pressure on the surrounding territorial matrix and thereby caused the expansion of hypertrophic lacunae. To assess this possibility, segments of the growth plate were placed in organ culture under different conditions. Under normal culture conditions, a band of hyaluronan staining migrated across the segments coinciding with the enlargement of lacunae in these regions, and the segments, as a whole, increased in size. In contrast, when the segments were cultured in the presence of hyaluronidase, which degraded the pericellular hyaluronan, the lacunae did not undergo enlargement and the overall size of the segments did not increase. These results suggest that the production of hyaluronan contributes to the enlargement of hypertrophic lacunae which is important for determining both the body's stature and proportions.

scholarly journals ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes

2013 ◽  
Vol 33 (16) ◽  
pp. 3077-3090 ◽  
Author(s):  
Katherine C. Hall ◽  
Daniel Hill ◽  
Miguel Otero ◽  
Darren A. Plumb ◽  
Dara Froemel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Terminal Differentiation ◽  
Cell Interactions ◽  
Hypertrophic Chondrocytes ◽  
Main Role ◽  
Egfr Signaling ◽  
Cell Cell

Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes (A17ΔCh) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported byin vitroexperiments showing enhanced hypertrophic differentiation of primary chondrocytes lackingAdam17. The enlarged zone of hypertrophic chondrocytes inA17ΔChmice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor α (TGFα), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGFα/EGFR signaling axis.

scholarly journals Immunolocation analysis of glycosaminoglycans in the human growth plate.

1992 ◽  
Vol 40 (2) ◽  
pp. 275-282 ◽  
Author(s):  
S Byers ◽  
B Caterson ◽  
J J Hopwood ◽  
B K Foster
Keyword(s):  
Extracellular Matrix ◽  
Growth Plate ◽  
Dermatan Sulfate ◽  
Human Growth ◽  
Keratan Sulfate ◽  
The Other ◽  
Hypertrophic Chondrocytes ◽  
Proliferative Zone ◽  
Metabolic Products ◽  
Metaphyseal Bone

Monoclonal antibodies were used in this study to immunolocate glycosaminoglycans throughout the human growth plate. Chondroitin-4-sulfate, chondroitin-6-sulfate, and keratan sulfate were observed in the extracellular matrix of all zones of the growth plate and persisted into the cartilage trabeculae of newly formed metaphyseal bone. Also present in the extracellular matrix was an oversulfated chondroitin/dermatan sulfate glycosaminoglycan which appeared to be specific to the proliferative and hypertrophic zones of the growth plate. As with the other extracellular matrix molecules, this epitope persisted into the cartilage trabeculae of the metaphyseal bone. Zonal differences between the extracellular and pericellular or lacunae matrix were also observed. The hypertrophic chondrocytes appeared to synthesize chondroitin sulfate chains containing a non-reducing terminal 6-sulfated disaccharide, which were located in areas immediately adjacent to the cells. This epitope was not found to any significant extent in the other zones. The pericellular region around hypertrophic chondrocytes also contained a keratan sulfate epitope which was also observed in the resting zone but not in the proliferative zone. These cell-associated glycosaminoglycans were not found in the cartilage trabeculae of metaphyseal bone, indicating their removal as the terminal hypertrophic chondrocytes and their lacunae are removed by invading blood vessels. These changes in matrix glycosaminoglycan content, both in the different zones and within zones, indicate constant subtle alterations in chondrocyte metabolic products as they proceed through their life cycle of proliferation, maturation, and hypertrophy.

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