scholarly journals Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate

2004 ◽  
Vol 164 (5) ◽  
pp. 747-758 ◽  
Author(s):  
Patrick Smits ◽  
Peter Dy ◽  
Srijeet Mitra ◽  
Véronique Lefebvre

Sox5 and Sox6 encode Sry-related transcription factors that redundantly promote early chondroblast differentiation. Using mouse embryos with three or four null alleles of Sox5 and Sox6, we show that they are also essential and redundant in major steps of growth plate chondrocyte differentiation. Sox5 and Sox6 promote the development of a highly proliferating pool of chondroblasts between the epiphyses and metaphyses of future long bones. This pool is the likely cellular source of growth plates. Sox5 and Sox6 permit formation of growth plate columnar zones by keeping chondroblasts proliferating and by delaying chondrocyte prehypertrophy. They allow induction of chondrocyte hypertrophy and permit formation of prehypertrophic and hypertrophic zones by delaying chondrocyte terminal differentiation induced by ossification fronts. They act, at least in part, by down-regulating Ihh signaling, Fgfr3, and Runx2 and by up-regulating Bmp6. In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones.

2015 ◽  
Vol 30 (9) ◽  
pp. 1560-1571 ◽  
Author(s):  
Kenji Kato ◽  
Pallavi Bhattaram ◽  
Alfredo Penzo‐Méndez ◽  
Abhilash Gadi ◽  
Véronique Lefebvre

2014 ◽  
Vol 116 (4) ◽  
pp. 425-438 ◽  
Author(s):  
Maria A. Serrat ◽  
Morgan L. Efaw ◽  
Rebecca M. Williams

Advances in understanding the molecular regulation of longitudinal growth have led to development of novel drug therapies for growth plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents to avascular-cartilage plates. Dense extracellular matrix and lack of penetrating blood vessels create a semipermeable “barrier,” which hinders molecular transport at the vascular-cartilage interface. To overcome this obstacle, we used a hindlimb heating model to manipulate bone circulation in 5-wk-old female mice ( n = 22). Temperatures represented a physiological range of normal human knee joints. We used in vivo multiphoton microscopy to quantify temperature-enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22°C to 34°C increases vascular access of large systemic molecules, modeled using 10, 40, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from subperichondrial plexus vessels and accumulation in growth plate cartilage. Growth plate entry of 10 kDa dextrans increased >150% at 34°C. Entry of 40 and 70 kDa dextrans increased <50%, suggesting a size-dependent temperature enhancement. Total dextran levels in the plexus increased at 34°C, but relative leakage out of vessels was not temperature dependent. Blood velocity and vessel diameter increased 118% and 31%, respectively, at 34°C. These results demonstrate that heat enhances vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive strategy for modulating delivery of therapeutics to impaired growth plates of children.


1996 ◽  
Vol 11 (10) ◽  
pp. 2008-2016 ◽  
Author(s):  
P. Urena ◽  
A. Ferreira ◽  
C. Morieux ◽  
T. Drueke ◽  
M. Christine de Vernejoul

2005 ◽  
Vol 284 (2) ◽  
pp. 311-322 ◽  
Author(s):  
Jishuai Zhang ◽  
Xiaohong Tan ◽  
Wenlong Li ◽  
Youliang Wang ◽  
Jian Wang ◽  
...  

2015 ◽  
Vol 104 (2) ◽  
pp. 357-366 ◽  
Author(s):  
Jakub Jaroszewicz ◽  
Anna Kosowska ◽  
Dietmar Hutmacher ◽  
Wojciech Swieszkowski ◽  
Stanisław Moskalewski

2006 ◽  
Vol 126 (6) ◽  
pp. 713-722 ◽  
Author(s):  
Ronald R. Gomes ◽  
Toin H. Kuppevelt ◽  
Mary C. Farach-Carson ◽  
Daniel D. Carson

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