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Direct Transformation of Chondrocytes into Bone Cells: Outside of the Box
Author(s) -
Feng Jerry
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.223.3
Subject(s) - endochondral ossification , aggrecan , chondrogenesis , cartilage , chondrocyte , microbiology and biotechnology , epiphysis , bone cell , chemistry , biology , anatomy , pathology , osteoarthritis , medicine , alternative medicine , articular cartilage
It has been widely accepted that hypertrophic chondrocytes undergo apoptosis prior to endochondral bone formation during limb development and long bone growth. Furthermore, it is generally believed that chondrogenesis is a separate physiological process from osteogenesis, although both processes are closely linked. However, new studies suggest that chondrocytes directly transform into bone cells during long bone formation using a cell lineage tracing approach. To extend the current study, we initially revealed only modest numbers of apoptotic cells but high levels of anti‐apoptotic Bcl ‐2 expression in hypertrophic chondrocytes of growth plates, indicating that most of hypertrophic chondrocytes do not go apoptosis. Next, we revealed dividing hypertrophic chondrocytes by BrdU staining, and high alkaline phosphatase activity (early bone marker). Furthermore, e x vivo culture of newborn cartilage on a chick chorioallantoic membrane showed that after 5 days the cells on the periphery of the explants had begun to express Col1 (bone marker) and to produce bone‐like matrices. The cartilage‐specific cell lineage tracing approach in triple mice containing Rosa 26 tdTomato (tracing marker), 2.3 Col 1 GFP (bone cell marker), and Aggrecan Cre ERT2 (one‐time Tamoxifen‐induced) or Col10‐ Cre (activated from E14.5 throughout adult stage) proved the direct transformation of chondrocytes into bone cells in vivo . Importantly, deletion of Bmpr1a in chondrocytes (via crossing Bmpr1a and Aggrecan Cre ERT2 with one‐time Tamoxifen‐induction) leads to a lack of metaphysis, delayed ossification and malformed epiphysis. As a result, these mice displayed a short status and deformed knee joint. This finding supports the novel concept that the chondrogenesis is an initial phase of endochondrogenesis (phase one to build a health cartilage template for future bone formation), in which some of these chondrocytes go apoptosis, some divide, and many of them become bone cells. In phase two, most chondrocytes directly transform into bone. Taken together, this multi‐pronged approach not only demonstrates that a majority of chondrocytes directly transform into bone cells, but also challenge the dogma that chondrogenesis is a separated process from osteogenesis during endochondral bone formation. Support or Funding Information (This study was partially supported by NIH grants DE025014 and R56DE022789 to JQF).