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Transdifferentiation of Chondrocytes to Osteoblasts during Bone Fracture Healing
Author(s) -
Marcucio Ralph,
Hu Diane,
Yang Frank,
Bahney Chelsea,
Miclau Theodore
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.223.1
Subject(s) - endochondral ossification , chondrogenesis , intramembranous ossification , cartilage , microbiology and biotechnology , bone healing , transdifferentiation , osteoblast , bone cell , chemistry , anatomy , ossification , mesenchymal stem cell , progenitor cell , pathology , stem cell , biology , medicine , biochemistry , in vitro
For more than 150 years, dogma has been that cartilage is replaced by bone during endochondral ossification. This is thought to be true during development and this process is recapitulated during repair of fractured bones. During endochondral ossification mesenchymal cells condense and differentiate into chondrocytes. The chondrocytes mature, become hypertrophic, and induce vascular invasion of the cartilage matrix. The currently accepted model states that chondrocytes undergo apoptosis and osteoblast progenitor cells are delivered to the cartilage by the invading vasculature to replace the cartilage with bone. However, recent data from our laboratory indicates that this model is incorrect. Chondrocytes undergo a transformation during bone fracture healing to become osteoblasts that make the new bone matrix. This process occurs in a region that we named “the transition zone” that is located adjacent to the invading vasculature. Chondrocytes located in the transition have two fates. Some of the chondrocytes die, while others re‐enter the cell cycle, switch off the chondrogenic program, activate the molecular program associated with pluripotency, activate the molecular program associated with osteogenesis, and synthesize new bone matrix via perilacunar remodeling, possibly in response to signals from the invading vasculature. Others have recognized this process in many contexts. In fact, in the early to middle 1800's metaplasia of cartilage to bone was considered to be the mechanism of bone formation. Our data support this model and indicate that the main process of bone formation is by direct transformation of chondrocytes to osteoblasts during bone fracture healing. Support or Funding Information NIH: NIAMS: F32AR062469 to C.B., R01‐AR057344 to T.M., NIA: R01‐AG046282 to R.M. MTF Junior Investigator Award to C.B.