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 Role of iRhoms 1 and 2 in Endochondral Ossification

2020 ◽  
Vol 21 (22) ◽  
pp. 8732
Author(s):  
Renpeng Fang ◽  
Coline Haxaire ◽  
Miguel Otero ◽  
Samantha Lessard ◽  
Gisela Weskamp ◽  
...  
Keyword(s):  
Growth Plate ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Egf Receptor ◽  
Hypertrophic Chondrocytes ◽  
Egfr Mutations ◽  
Appendicular Skeleton ◽  
Growth Plates ◽  
Egfr Ligands

Growth of the axial and appendicular skeleton depends on endochondral ossification, which is controlled by tightly regulated cell–cell interactions in the developing growth plates. Previous studies have uncovered an important role of a disintegrin and metalloprotease 17 (ADAM17) in the normal development of the mineralized zone of hypertrophic chondrocytes during endochondral ossification. ADAM17 regulates EGF-receptor signaling by cleaving EGFR-ligands such as TGFα from their membrane-anchored precursor. The activity of ADAM17 is controlled by two regulatory binding partners, the inactive Rhomboids 1 and 2 (iRhom1, 2), raising questions about their role in endochondral ossification. To address this question, we generated mice lacking iRhom2 (iR2−/−) with floxed alleles of iRhom1 that were specifically deleted in chondrocytes by Col2a1-Cre (iR1∆Ch). The resulting iR2−/−iR1∆Ch mice had retarded bone growth compared to iR2−/− mice, caused by a significantly expanded zone of hypertrophic mineralizing chondrocytes in the growth plate. Primary iR2−/−iR1∆Ch chondrocytes had strongly reduced shedding of TGFα and other ADAM17-dependent EGFR-ligands. The enlarged zone of mineralized hypertrophic chondrocytes in iR2−/−iR1∆Ch mice closely resembled the abnormal growth plate in A17∆Ch mice and was similar to growth plates in Tgfα−/− mice or mice with EGFR mutations. These data support a model in which iRhom1 and 2 regulate bone growth by controlling the ADAM17/TGFα/EGFR signaling axis during endochondral ossification.

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.

Distribution of hyaluronan in the epiphysial growth plate: turnover by CD44-expressing osteoprogenitor cells

1994 ◽  
Vol 107 (10) ◽  
pp. 2669-2677 ◽  
Author(s):  
P. Pavasant ◽  
T.M. Shizari ◽  
C.B. Underhill
Keyword(s):  
Monoclonal Antibody ◽  
Growth Plate ◽  
Cultured Cells ◽  
Human Cell Line ◽  
Histochemical Staining ◽  
Long Bone ◽  
Thin Sections ◽  
Osteoprogenitor Cells ◽  
Double Label ◽  
Mouse Tibia

In the present study, we have examined the distribution of both hyaluronan and its receptor, CD44, during the process of endochondral ossification in the mouse tibia. Histochemical staining revealed that a large amount of hyaluronan was present in the lacunae located in the zone of hypertrophy, but it was greatly reduced or absent from the zone of erosion. In addition, hyaluronan was present in the cytoplasm of osteoprogenitor cells located in the zone of erosion. These cells also expressed CD44 on their surfaces, as revealed by double-label immunohistochemistry. These results suggested that the osteoprogenitor cells may use CD44 to bind and internalize hyaluronan, and subsequently degrade it with lysosomal enzymes. To test this possibility, we examined the human cell line, MG-63, which closely resembles osteoprogenitor cells. These cells produced several different forms of CD44, as determined by western blotting (85, 116 and 150 kDa). In addition, the binding of isotopically labeled hyaluronan to detergent extracts of these cells was blocked by a monoclonal antibody to CD44. Similarly, the degradation of hyaluronan by these cultured cells was also inhibited by a monoclonal antibody to CD44. To determine if these cells could remove hyaluronan from the growth plate, the cells were cultured directly on top of thin sections of the epiphysial region of long bone. After 16 hours, the sections were stained for hyaluronan. The MG-63 cells removed significant amounts of hyaluronan present in the zone of hypertrophy, and this effect was blocked by an excess of soluble hyaluronan and by a monoclonal antibody to CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization

2005 ◽  
Vol 98 (6) ◽  
pp. 2381-2389 ◽  
Author(s):  
A. Reich ◽  
N. Jaffe ◽  
A. Tong ◽  
I. Lavelin ◽  
O. Genina ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Growth Plate ◽  
Developmental Process ◽  
Mechanical Strain ◽  
Cell Counting ◽  
Mechanical Stimuli ◽  
Growth Plates ◽  
Average Width ◽  
The Matrix ◽  
Weight Loading

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 ± 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

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

scholarly journals Cam morphology in young male football players mostly develops before proximal femoral growth plate closure: a prospective study with 5-yearfollow-up

2018 ◽  
Vol 53 (9) ◽  
pp. 532-538 ◽  
Author(s):  
Pim van Klij ◽  
Marinus P Heijboer ◽  
Abida Z Ginai ◽  
Jan A N Verhaar ◽  
Jan H Waarsing ◽  
...  
Keyword(s):  
Growth Plate ◽  
Alpha Angle ◽  
Football Players ◽  
Growth Plates ◽  
Time Points ◽  
Open Growth Plate ◽  
Morphology Development ◽  
Open Growth ◽  
Cam Morphology

ObjectivesCam morphology is not completely understood. The aim of this study was threefold: (1) to investigate if cam morphology development is associated with growth plate status; (2) to examine whether cam morphology continues to develop after growth plate closure; and (3) to qualitatively describe cam morphology development over 5-year follow-up.MethodsAcademy male football players (n=49) participated in this prospective 5-year follow-up study (baseline 12–19 years old). Anteroposterior and frog-leg lateral views were obtained at baseline (142 hips), 2.5-year (126 hips) and 5-year follow-up (98 hips). Cam morphology on these time points was defined as: (A) visual scores of the anterior head-neck junction, classified as: (1) normal, (2) flattening, and (3) prominence; and (B) alpha angle ≥60°. Proximal femoral growth plates were classified as open or closed. Cam morphology development was defined as every increase in visual score and/or increase in alpha angle from <60° to ≥60°, between two time points. This resulted in 224 measurements for cam morphology development analysis.ResultsCam morphology development was significantly associated with open growth plates based on visual score (OR: 10.03, 95% CI 3.49 to 28.84, p<0.001) and alpha angle (OR: 2.85, 95% CI 1.18 to 6.88, p=0.020). With both definitions combined, cam developed in 104 of 142 hips during follow-up. Of these 104 hips, cam developed in 86 hips (82.7%) with open growth plate and in 18 hips (17.3%) with a closed growth plate. Cam morphology developed from 12 to 13 years of age until growth plate closure around 18 years.ConclusionCam morphology of the hip is more likely to develop with an open growth plate.

scholarly journals Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1820-1828 ◽  
Author(s):  
Rose Marino ◽  
Anita Hegde ◽  
Kevin M. Barnes ◽  
Lenneke Schrier ◽  
Joyce A. Emons ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Inhibition ◽  
Growth Plate ◽  
Bone Growth ◽  
Structural Characteristics ◽  
Linear Growth Rate ◽  
Growth Plate Chondrocytes ◽  
Growth Plates ◽  
Catch Up ◽  
Growth Inhibiting

Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.

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
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