Yan Jing, Junjun Jing, Ling Ye, Xiaohua Liu, Stephen E Harris, Robert J Hinton, Jian Q Feng
Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre in early cartilage cells with a one-time tamoxifen injection. We observed the absence of lineage progression of chondrocyte-derived bone cells to form osteoblasts and osteocytes in metaphyses. Furthermore, we demonstrated the key contribution of growth plate chondrocytes and articular chondrocytes, not only for long bone growth, but also for bone remodeling. In contrast, deleting Bmpr1a in early osteoblasts with 3.6 Col 1-Cre had little impact on skeletal shape and size except for a sharp increase in osteoblasts and osteocytes, leading to a profound increase in bone volume. We conclude that chondrogenesis and osteogenesis are one continuous developmental and lineage-defined biological process, in which Bmpr1a signaling in chondrocytes is necessary for the formation of a pool or niche of osteoprogenitors that then contributes in a major way to overall bone formation and growth.
Genes Dev. 2002 Jun 15;16(12):1446-65
[PMID:
12080084]
Birth Defects Res C Embryo Today. 2005 Dec;75(4):330-9
[PMID:
16425255]
Bone. 2002 Dec;31(6):654-60
[PMID:
12531558]
J Bone Miner Res. 2011 Feb;26(2):331-40
[PMID:
20734454]
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14665-70
[PMID:
16203988]
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5062-7
[PMID:
15781876]
Development. 2008 Nov;135(22):3801-11
[PMID:
18927151]
Development. 2016 Jan 15;143(2):339-47
[PMID:
26657771]
Connect Tissue Res. 2014 Aug;55 Suppl 1:73-8
[PMID:
25158185]
Cell Res. 2014 Oct;24(10):1266-9
[PMID:
25145361]
J Dent Res. 2015 Dec;94(12 ):1668-75
[PMID:
26341973]
Genesis. 2002 Feb;32(2):69-72
[PMID:
11857780]
Bone Miner. 1992 Oct;19(1):1-20
[PMID:
1422302]
Int J Dev Biol. 2004 Sep;48(7):645-53
[PMID:
15470637]
J Cell Sci. 2011 Oct 15;124(Pt 20):3428-40
[PMID:
21984813]
Genesis. 2009 Dec;47(12):805-14
[PMID:
19830818]
J Bone Miner Res. 2002 Oct;17(10):1822-31
[PMID:
12369786]
Clin Orthop Relat Res. 1977 Nov-Dec;(129):299-304
[PMID:
608290]
J Dent Res. 2015 Dec;94(12 ):1625-7
[PMID:
26341975]
Development. 2006 Dec;133(23):4667-78
[PMID:
17065231]
J Dent Res. 2017 Jan;96(1):23-30
[PMID:
27664203]
Biol Open. 2015 Apr 16;4(5):608-21
[PMID:
25882555]
Int J Biol Sci. 2013 Sep 18;9(9):895-906
[PMID:
24163588]
J Bone Miner Res. 2014 Nov;29(11):2307-22
[PMID:
25264148]
Microsc Res Tech. 1998 Oct 15;43(2):191-204
[PMID:
9823004]
Nat Genet. 2006 Nov;38(11):1310-5
[PMID:
17033621]
PLoS Genet. 2006 Dec;2(12):e216
[PMID:
17194222]
J Vis Exp. 2016 Dec 28;(118):
[PMID:
28060349]
PLoS Genet. 2014 Dec 04;10(12):e1004820
[PMID:
25474590]
J Bone Miner Res. 2008 Dec;23(12):2007-17
[PMID:
18684091]
Nat Cell Biol. 2014 Dec;16(12):1157-67
[PMID:
25419849]
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12097-102
[PMID:
25092332]
Medicina (Kaunas). 2008;44(9):673-7
[PMID:
18971604]
J Bone Miner Res. 2011 May;26(5):1047-56
[PMID:
21542006]
Nature. 2003 May 15;423(6937):332-6
[PMID:
12748651]
J Histochem Cytochem. 2005 May;53(5):593-602
[PMID:
15872052]
Connect Tissue Res. 2014 Aug;55 Suppl 1:129-33
[PMID:
25158197]
Mol Cell Biol. 2010 Jun;30(12):3071-85
[PMID:
20404086]
