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Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation.

Yuan X, Yang S - PLoS ONE (2015)

Bottom Line: Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development.Loss of IFT80 in the embryonic stage resulted in short limbs at birth.These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University of Buffalo, State University of New York, Buffalo, NY, United States of America.

ABSTRACT
Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation.

No MeSH data available.


Related in: MedlinePlus

Endochondral bone ossification was examined of the tibial growth plates of newborn IFT80f/f mice and Col2α1; IFT80f/f mice using Alizarin Red/Von Kossa staining.Mice exposed to tamoxifen at E14.5, E16.5, and E18.5. (A) Alizarin Red staining of the tibial section. Bone volume (BV) and tissue volume (TV) were quantified using Image J (n = 3). (B) Von Kossa staining of the tibial section. Fast green was used as a counter stain. BV/TV were quantified using Image J (n = 3).
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pone.0130618.g003: Endochondral bone ossification was examined of the tibial growth plates of newborn IFT80f/f mice and Col2α1; IFT80f/f mice using Alizarin Red/Von Kossa staining.Mice exposed to tamoxifen at E14.5, E16.5, and E18.5. (A) Alizarin Red staining of the tibial section. Bone volume (BV) and tissue volume (TV) were quantified using Image J (n = 3). (B) Von Kossa staining of the tibial section. Fast green was used as a counter stain. BV/TV were quantified using Image J (n = 3).

Mentions: To further study the role of IFT80 in endochondral bone formation, we performed histological analysis, Alizarin red staining and Von Kossa staining to analyze endochondral bone ossification. We found the trabecular bone volume was decreased in Col2α1; IFT80f/f mice (S2 Fig). Additionally, there was no significant difference in the mineralization capability of periochondal cells, as the bone collar formation was not affected (Fig 3A and 3B). However, the bone matrix and mineralization, as well as the trabecular bone volume, were dramatically decreased in Col2α1; IFT80f/f mice (Fig 3A and 3B). These results suggest that IFT80 is required for chondrogenesis and endochondral bone formation in the embryonic stage.


Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation.

Yuan X, Yang S - PLoS ONE (2015)

Endochondral bone ossification was examined of the tibial growth plates of newborn IFT80f/f mice and Col2α1; IFT80f/f mice using Alizarin Red/Von Kossa staining.Mice exposed to tamoxifen at E14.5, E16.5, and E18.5. (A) Alizarin Red staining of the tibial section. Bone volume (BV) and tissue volume (TV) were quantified using Image J (n = 3). (B) Von Kossa staining of the tibial section. Fast green was used as a counter stain. BV/TV were quantified using Image J (n = 3).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476593&req=5

pone.0130618.g003: Endochondral bone ossification was examined of the tibial growth plates of newborn IFT80f/f mice and Col2α1; IFT80f/f mice using Alizarin Red/Von Kossa staining.Mice exposed to tamoxifen at E14.5, E16.5, and E18.5. (A) Alizarin Red staining of the tibial section. Bone volume (BV) and tissue volume (TV) were quantified using Image J (n = 3). (B) Von Kossa staining of the tibial section. Fast green was used as a counter stain. BV/TV were quantified using Image J (n = 3).
Mentions: To further study the role of IFT80 in endochondral bone formation, we performed histological analysis, Alizarin red staining and Von Kossa staining to analyze endochondral bone ossification. We found the trabecular bone volume was decreased in Col2α1; IFT80f/f mice (S2 Fig). Additionally, there was no significant difference in the mineralization capability of periochondal cells, as the bone collar formation was not affected (Fig 3A and 3B). However, the bone matrix and mineralization, as well as the trabecular bone volume, were dramatically decreased in Col2α1; IFT80f/f mice (Fig 3A and 3B). These results suggest that IFT80 is required for chondrogenesis and endochondral bone formation in the embryonic stage.

Bottom Line: Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development.Loss of IFT80 in the embryonic stage resulted in short limbs at birth.These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University of Buffalo, State University of New York, Buffalo, NY, United States of America.

ABSTRACT
Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation.

No MeSH data available.


Related in: MedlinePlus