TY - JOUR
T1 - Chondrocytes directly transform into bone cells in mandibular condyle growth
AU - Jing, Y.
AU - Zhou, X.
AU - Han, X.
AU - Jing, J.
AU - Von Der Mark, K.
AU - Wang, J.
AU - De Crombrugghe, B.
AU - Hinton, R. J.
AU - Feng, J. Q.
N1 - Funding Information:
This study was partially supported by National Institutes of Health grants DE025014 and R56DE022789 to J.Q.F. and by National Natural Science Foundation of China grant 81371172 to X.H.
Publisher Copyright:
© International & American Associations for Dental Research 2015.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - For decades, it has been widely accepted that hypertrophic chondrocytes undergo apoptosis prior to endochondral bone formation. However, very recent studies in long bone suggest that chondrocytes can directly transform into bone cells. Our initial in vivo characterization of condylar hypertrophic chondrocytes revealed modest numbers of apoptotic cells but high levels of antiapoptotic Bcl-2 expression, some dividing cells, and clear alkaline phosphatase activity (early bone marker). Ex vivo culture of newborn condylar cartilage on a chick chorioallantoic membrane showed that after 5 d the cells on the periphery of the explants had begun to express Col1 (bone marker). The cartilage-specific cell lineage-tracing approach in triple mice containing Rosa 26tdTomato (tracing marker), 2.3 Col1GFP (bone cell marker), and aggrecan CreERT2 (onetime tamoxifen induced) or Col10-Cre (activated from E14.5 throughout adult stage) demonstrated the direct transformation of chondrocytes into bone cells in vivo. This transformation was initiated at the inferior portion of the condylar cartilage, in contrast to the initial ossification site in long bone, which is in the center. Quantitative data from the Col10-Cre compound mice showed that hypertrophic chondrocytes contributed to ∼80% of bone cells in subchondral bone, ∼70% in a somewhat more inferior region, and ∼40% in the most inferior part of the condylar neck (n = 4, P < 0.01 for differences among regions). This multipronged approach clearly demonstrates that a majority of chondrocytes in the fibrocartilaginous condylar cartilage, similar to hyaline cartilage in long bones, directly transform into bone cells during endochondral bone formation. Moreover, ossification is initiated from the inferior portion of mandibular condylar cartilage with expansion in one direction.
AB - For decades, it has been widely accepted that hypertrophic chondrocytes undergo apoptosis prior to endochondral bone formation. However, very recent studies in long bone suggest that chondrocytes can directly transform into bone cells. Our initial in vivo characterization of condylar hypertrophic chondrocytes revealed modest numbers of apoptotic cells but high levels of antiapoptotic Bcl-2 expression, some dividing cells, and clear alkaline phosphatase activity (early bone marker). Ex vivo culture of newborn condylar cartilage on a chick chorioallantoic membrane showed that after 5 d the cells on the periphery of the explants had begun to express Col1 (bone marker). The cartilage-specific cell lineage-tracing approach in triple mice containing Rosa 26tdTomato (tracing marker), 2.3 Col1GFP (bone cell marker), and aggrecan CreERT2 (onetime tamoxifen induced) or Col10-Cre (activated from E14.5 throughout adult stage) demonstrated the direct transformation of chondrocytes into bone cells in vivo. This transformation was initiated at the inferior portion of the condylar cartilage, in contrast to the initial ossification site in long bone, which is in the center. Quantitative data from the Col10-Cre compound mice showed that hypertrophic chondrocytes contributed to ∼80% of bone cells in subchondral bone, ∼70% in a somewhat more inferior region, and ∼40% in the most inferior part of the condylar neck (n = 4, P < 0.01 for differences among regions). This multipronged approach clearly demonstrates that a majority of chondrocytes in the fibrocartilaginous condylar cartilage, similar to hyaline cartilage in long bones, directly transform into bone cells during endochondral bone formation. Moreover, ossification is initiated from the inferior portion of mandibular condylar cartilage with expansion in one direction.
KW - cell lineage tracing
KW - cell transformation
KW - development
KW - osteoblast
KW - osteocyte
KW - temporomandibular joint
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U2 - 10.1177/0022034515598135
DO - 10.1177/0022034515598135
M3 - Article
C2 - 26341973
AN - SCOPUS:84948395489
SN - 0022-0345
VL - 94
SP - 1668
EP - 1675
JO - Journal of Dental Research
JF - Journal of Dental Research
IS - 12
ER -