scholarly journals Inhibitory function of parathyroid hormone-related protein on chondrocyte hypertrophy: the implication for articular cartilage repair

2012 ◽  
Vol 14 (4) ◽  
Author(s):  
Wei Zhang ◽  
Jialin Chen ◽  
Shufang Zhang ◽  
Hong Wei Ouyang
Keyword(s):  
Parathyroid Hormone ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Related Protein ◽  
Chondrocyte Hypertrophy ◽  
Articular Cartilage Repair ◽  
Inhibitory Function ◽  
Parathyroid Hormone Related Protein

Expression of parathyroid hormone-related protein in rat articular cartilage

1995 ◽  
Vol 57 (3) ◽  
pp. 196-200 ◽  
Author(s):  
T. Tsukazaki ◽  
A. Ohtsuru ◽  
H. Enomoto ◽  
H. Yano ◽  
K. Motomura ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Articular Cartilage ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

scholarly journals Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF-β Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Rui Dong ◽  
Jun Ying ◽  
Taotao Xu ◽  
Songfeng Hu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Defect ◽  
Cartilage Degradation ◽  
Matrix Degradation ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Articular Cartilage Repair ◽  
Genes Expression ◽  
Cells Cultured

Objective. To investigate the effect and underlying mechanism of Bushenhuoxue (BSHX) formula on articular cartilage repair. Methods. Twenty-four full-thickness cartilage defect rats were divided into two groups: model group and BSHX group (treated with BSHX formula). Macroscopic observation and histopathological study were conducted after 4- and 8-week treatment. Additionally, we also evaluated chondrocyte proliferation, extracellular matrix (ECM) deposition, cartilage degradation, and chondrocyte hypertrophy-related genes expression in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Moreover, we assessed aforementioned genes expression and pSMAD2/3 protein level in Tgfβr2 siRNA transfected chondrogenic ATDC5 cells in order to address whether BSHX formula exerts cartilage repairing effect through TGF-β signaling. Results. Neocartilage regeneration promotion effect was observed in cartilage defect rats after BSHX formula treatment, with increases in Col2 and pSMAD2 and decreases in Mmp13 and Runx2. Moreover, cell proliferation, the elevated Col2a1, Aggrecan and pSMAD2/3, reduced Mmp13, Adamts5, Col10a1, and Runx2 expression were also observed in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Besides, the expression alteration of ECM deposition, cartilage degradation, chondrocyte hypertrophy-related genes, and pSMAD2/3 protein levels presented in Tgfβr2 downregulated chondrogenic ATDC5 cells couldn’t be adjusted by BSHX formula treatment. Conclusion. By activation of TGF-β signaling, BSHX formula can promote articular cartilage repair by accelerating chondrocyte proliferation and maintaining chondrocyte phenotype, upregulate ECM accumulation, and inhibit matrix degradation.

Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 543-548 ◽  
Author(s):  
S.J. Karp ◽  
E. Schipani ◽  
B. St-Jacques ◽  
J. Hunzelman ◽  
H. Kronenberg ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Critical Role ◽  
Receptor Activation ◽  
Indian Hedgehog ◽  
Appendicular Skeleton ◽  
Null Mutation ◽  
Related Protein ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Parathyroid Hormone Related Protein

Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton. Targeted deletion of Ihh results in short-limbed dwarfism, with decreased chondrocyte proliferation and extensive hypertrophy, features shared by mutants in PTHrP and its receptor. Activation of Ihh signaling upregulates PTHrP at the articular surface and prevents chondrocyte hypertrophy in wild-type but not PTHrP null explants, suggesting that Ihh acts through PTHrP. To investigate the relationship between these factors during development of the appendicular skeleton, mice were produced with various combinations of an Ihh null mutation (Ihh(−/−)), a PTHrP null mutation (PTHrP(−/−)), and a constitutively active PTHrP/Parathyroid hormone Receptor expressed under the control of the Collagen II promoter (PTHrPR*). PTHrPR* rescues PTHrP(−/−) embryos, demonstrating this construct can completely compensate for PTHrP signalling. At 18.5 dpc, limb skeletons of Ihh, PTHrP compound mutants were identical to Ihh single mutants suggesting Ihh is necessary for PTHrP function. Expression of PTHrPR* in chondrocytes of Ihh(−/−) mice prevented premature chondrocyte hypertrophy but did not rescue either the short-limbed dwarfism or decreased chondrocyte proliferation. These experiments demonstrate that the molecular mechanism that prevents chondrocyte hypertrophy is distinct from that which drives proliferation. Ihh positively regulates PTHrP, which is sufficient to prevent chondrocyte hypertrophy and maintain a normal domain of cells competent to undergo proliferation. In contrast, Ihh is necessary for normal chondrocyte proliferation in a pathway that can not be rescued by PTHrP signaling. This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions.

Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes

2013 ◽  
Vol 125 (10) ◽  
pp. 461-470 ◽  
Author(s):  
Michele Pelosi ◽  
Stefano Lazzarano ◽  
Brendan L. Thoms ◽  
Chris L. Murphy
Keyword(s):  
Parathyroid Hormone ◽  
Articular Cartilage ◽  
Growth Plate ◽  
Articular Chondrocytes ◽  
Human Articular Chondrocytes ◽  
Long Bone ◽  
Human Articular Cartilage ◽  
Dependent Manner ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

PTHrP (parathyroid hormone-related protein) is crucial for normal cartilage development and long bone growth and acts to delay chondrocyte hypertrophy and terminal differentiation in the growth plate. After growth plate closure adult HACs (human articular chondrocytes) still produce PTHrP, suggesting a possible role for this factor in the permanent articular cartilage. However, the expression regulation and function of PTHrP in the permanent articular cartilage is unknown. Human articular cartilage is an avascular tissue and functions in a hypoxic environment. The resident chondrocytes have adapted to hypoxia and use it to drive their tissue-specific functions. In the present study, we explored directly in normal articular chondrocytes isolated from a range of human donors the effect of hypoxia on PTHrP expression and whether PTHrP can regulate the expression of the permanent articular chondrocyte phenotype. We show that in HACs PTHrP is up-regulated by hypoxia in a HIF (hypoxia-inducible factor)-1α and HIF-2α-dependent manner. Using recombinant PTHrP, siRNA-mediated depletion of endogenous PTHrP and by blocking signalling through its receptor [PTHR1 (PTHrP receptor 1)], we show that hypoxia-induced PTHrP is a positive regulator of the key cartilage transcription factor SOX9 [SRY (sex determining region on the Y chromosome)-box 9], leading to increased COL2A1 (collagen type II, α1) expression. Our findings thus identify PTHrP as a potential factor for cartilage repair therapies through its ability to promote the differentiated HAC phenotype.

Parathyroid Hormone–Related Protein Inhibits Endothelin-1 Production

Hypertension ◽  
1996 ◽  
Vol 27 (3) ◽  
pp. 360-363 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
Michio Tamatani ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Endothelin 1 ◽  
Parathyroid Hormone Related Protein
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