Regulation of osteochondral remodeling by hypertrophic chondrocyte-derived factors during osteoarthritis

2021 ◽  
Vol 29 ◽  
pp. S197-S198
Author(s):  
I. Toillon ◽  
S. van Eegher ◽  
A. Pigenet ◽  
A. Cambon-Binder ◽  
A. Larsen ◽  
...  
Keyword(s):  
Hypertrophic Chondrocyte

Type VI collagen expression is upregulated in the early events of chondrocyte differentiation

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 245-251
Author(s):  
R. Quarto ◽  
B. Dozin ◽  
P. Bonaldo ◽  
R. Cancedda ◽  
A. Colombatti
Keyword(s):  
Suspension Culture ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Type Vi Collagen ◽  
Full Spectrum ◽  
Collagen Expression ◽  
Hypertrophic Chondrocyte

Dedifferentiated chondrocytes cultured adherent to the substratum proliferate and synthesize large amounts of type I collagen but when transferred to suspension culture they decrease proliferation, resume the chondrogenic phenotype and the synthesis of type II collagen, and continue their maturation to hypertrophic chondrocyte (Castagnola et al., 1986, J. Cell Biol. 102, 2310–2317). In this report, we describe the developmentally regulated expression of type VI collagen in vitro in differentiating avian chondrocytes. Type VI collagen mRNA is barely detectable in dedifferentiated chondrocytes as long as the attachment to the substratum is maintained, but increases very rapidly upon passage of the cells into suspension culture reaching a peak after 48 hours and declining after 5–6 days of suspension culture. The first evidence of a rise in the mRNA steady-state levels is obtained already at 6 hours for the alpha 3(VI) chain. Immunoprecipitation of metabolically labeled cells with type VI collagen antibodies reveals that the early mRNA rise is paralleled by an increased secretion of type VI collagen in cell media. Induction of type VI collagen is not the consequence of trypsin treatment of dedifferentiated cells since exposure to the actin-disrupting drug cytochalasin or detachment of the cells by mechanical procedures has similar effects. In 13-day-old chicken embryo tibiae, where the full spectrum of the chondrogenic differentiation process is represented, expression of type VI collagen is restricted to the articular cartilage where chondrocytes developmental stage is comparable to stage I (high levels of type II collagen expression).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of 5-Aza-2’ Deoxycytidine on Proliferation and Differentiation of Embryonic Chick Caudal Region Chondrocytes in Culture

2016 ◽  
Author(s):  
Samina Hyder Haq
Keyword(s):  
Cellular Differentiation ◽  
Rna Synthesis ◽  
Optimum Concentration ◽  
Embryonic Chick ◽  
Caudal Region ◽  
Cell Basis ◽  
Hypertrophic Chondrocyte ◽  
Epigenetic Factor ◽  
Proliferation And Differentiation ◽  
Differentiation Status

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2’ deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes

scholarly journals Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

2008 ◽  
Vol 2 (1) ◽  
pp. 121-125 ◽  
Author(s):  
K.D Evans ◽  
L.E Sheppard ◽  
D.I Grossman ◽  
S.H Rao ◽  
R.B Martin ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Growth Plate ◽  
Bone Growth ◽  
Cathepsin K ◽  
Chondrocyte Apoptosis ◽  
Cell Numbers ◽  
Hypertrophic Chondrocyte ◽  
Osteoclast Function ◽  
And Function

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate.

scholarly journals Pathology of Vitamin D Deficiency in Growing Turkeys

1986 ◽  
Vol 23 (4) ◽  
pp. 485-498 ◽  
Author(s):  
O. R. Hedstrom ◽  
N. F. Cheville ◽  
R. L. Horst
Keyword(s):  
Vitamin D ◽  
Structural Changes ◽  
Clinical Signs ◽  
Femoral Bone ◽  
Deficient Diet ◽  
Hypertrophic Chondrocyte ◽  
Turkey Poults ◽  
Bone Ash ◽  
Calcium Phosphorus ◽  
Plasma Alkaline Phosphatase

Turkey poults were fed a vitamin D-deficient diet and examined for clinical signs and structural changes of bone and parathyroid glands. Vitamin D-deficient poults developed ricketic changes during days 10 to 14. Control poults (deficient diet plus vitamin D) did not develop rickets. In deficient poults, lengths of proliferating-prehypertrophied zones of growth plates increased significantly in the proximal tibiotarsus but were only slightly elongated in the distal tibiotarsus. Unmineralized hypertrophic chondrocyte zones increased in length rapidly in conjunction with a decrease in the length of mineralized hypertrophic degenerative zones; this occurred more rapidly in proximal than in distal tibiotarsus. Other ricketic changes included decreases in bone ash, total femoral bone ash (calcium, phosphorus, magnesium), bone length, and body weight. Plasma alkaline phosphatase was increased, calcium was normal, and phosphorus was normal or elevated. Parathyroids were hyperplastic and had foci of degeneration. Vitamin D3 metabolites 25OHD3, 1,25(OH)2D3, and 24,25(OH)2D3 were rapidly depleted. Increase in bone ash Ca/P ratios in deficient poults suggests that phosphorus may be selectively released from ricketic bone. Low 25OHD3 and 1,25(OH)2D3 of control poults early in the experiment suggests that 1,400 IU of vitamin D3/kg of feed may not be an adequate level of vitamin D3 for growing turkey poults.

scholarly journals LRP5-deficiency in OsxCreERT2 mice models intervertebral disc degeneration by aging and compression

2019 ◽  
Author(s):  
Matthew J. Silva ◽  
Nilsson Holguin
Keyword(s):  
Transcription Factor ◽  
Intervertebral Disc ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Biomechanical Properties ◽  
Nucleus Pulposus Cells ◽  
Hypertrophic Chondrocyte ◽  
Age Related ◽  
Ivd Degeneration

ABSTRACTOsterix is a critical transcription factor of mesenchymal stem cell fate, where its loss or loss of WNT signaling diverts differentiation to a chondrocytic lineage. Intervertebral disc (IVD) degeneration activates differentiation of prehypertrophic chondrocyte-like cells and inactivates WNT signaling, but its interacting role with osterix is unclear. First, compared to young-adult (5mo), mechanical compression of old (18mo) IVD induced greater IVD degeneration. Aging (5 vs 12mo) and/or compression reduced the transcription of osterix and notochordal marker T by 40-75%. Compression elevated transcription of hypertrophic chondrocyte marker MMP13 and pre-osterix transcription factor RUNX2, but less so in 12mo IVD. Next, using an Ai9/td reporter and immunohistochemistry, annulus fibrosus and nucleus pulposus cells of 5mo IVD expressed osterix, but aging and compression reduced its expression. Lastly, in vivo LRP5-deficiency in osterix-expressing cells degenerated the IVD, inactivated WNT signaling, reduced the biomechanical properties by 45-70%, and reduced transcription of osterix, notochordal markers and chondrocytic markers by 60-80%. Overall, these data indicate that age-related inactivation of WNT signaling in osterix-expressing cells may limit regeneration by depleting progenitors and attenuating the expansion of chondrocyte-like cells.

scholarly journals The Receptor-Dependent Actions of 1,25-Dihydroxyvitamin D Are Required for Normal Growth Plate Maturation in NPt2a Knockout Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4607-4612 ◽  
Author(s):  
Susanne U. Miedlich ◽  
Eric D. Zhu ◽  
Yves Sabbagh ◽  
Marie B. Demay
Keyword(s):  
Vitamin D ◽  
Growth Plate ◽  
Fibroblast Growth Factor 23 ◽  
Normal Growth ◽  
Chondrocyte Apoptosis ◽  
Apoptotic Pathway ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Hypertrophic Chondrocyte

Rickets is a growth plate abnormality observed in growing animals and humans. Rachitic expansion of the hypertrophic chondrocyte layer of the growth plate, in the setting of hypophosphatemia, is due to impaired apoptosis of these cells. Rickets is observed in humans and mice with X-linked hypophosphatemia that is associated with renal phosphate wasting secondary to elevated levels of fibroblast growth factor-23. Rickets is also seen in settings of impaired vitamin D action, due to elevated PTH levels that increase renal phosphate excretion. However, mice with hypophosphatemia secondary to ablation of the renal sodium-dependent phosphate transport protein 2a (Npt2a), have not been reported to develop rickets. Because activation of the mitochondrial apoptotic pathway by phosphate is required for hypertrophic chondrocyte apoptosis in vivo, investigations were undertaken to address this paradox. Analyses of the Npt2a null growth plate demonstrate expansion of the hypertrophic chondrocyte layer at 2 wk of age, with resolution of this abnormality by 5 wk of age. This is temporally associated with an increase in circulating levels of 1,25-dihydroxyvitamin D. To address whether the receptor-dependent actions of this steroid hormone are required for normalization of the growth plate phenotype, the Npt2a null mice were mated with mice lacking the vitamin D receptor or were rendered vitamin D deficient. These studies demonstrate that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a normal growth plate phenotype in the Npt2a null mice.

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