1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, China.
2. Department of Biomedical Sciences, Texas A&M Baylor College of Dentistry, Dallas, TX, USA.
3. Department of Orthopaedic Surgery and Cell Biology, New York University School of Medicine, New York, NY, USA.
4. Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Dallas, TX, USA.
5. Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Bone morphogenic proteins (BMPs) are critical for both chondrogenesis and osteogenesis. Previous studies reported that embryos deficient in Bmp receptor (Bmpr)1a or Bmpr1b in cartilage display subtle skeletal defects; however, double mutant embryos develop severe skeletal defects, suggesting a functional redundancy that is essential for early chondrogenesis. In this study, we examined the postnatal role of Bmpr1a in cartilage. In the Bmpr1a conditional knockout (cKO, a cross between Bmpr1a flox and aggrecan-CreERT2 induced by a one-time-tamoxifen injection at birth and harvested at ages of 2, 4, 8 and 20 weeks), there was essentially no long bone growth with little expression of cartilage markers such as SOX9, IHH and glycoproteins. Unexpectedly, the null growth plate was replaced by bone-like tissues, supporting the notions that the progenitor cells in the growth plate, which normally form cartilage, can form other tissues such as bone and fibrous; and that BMPR1A determines the cell fate. A working hypothesis is proposed to explain the vital role of BMPR1A in postnatal chondrogenesis.
Keywords: BMPR1A, Growth plate, Cell fate, Chondrogenesis, Endochondral Bone.