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TGF‐b receptor II plays a vital role in neural crest‐derived osteogenesis but not in limb osteogenesis during postnatal development
Author(s) -
Xu Chunmei,
Wang Jun,
Xie Xudong,
Zhao Hu,
Carpenter Emily,
Feng Jian
Publication year - 2021
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.2021.35.s1.05019
Subject(s) - cortical bone , intramembranous ossification , osteoblast , cranial neural crest , chemistry , endocrinology , medicine , microbiology and biotechnology , anatomy , neural crest , biology , embryo , biochemistry , in vitro
It is widely accepted that TGF‐b signaling enhances osteogenesis via osteoprogenitor enrichment. However, removing TGF‐b receptor II ( Tgfbr2, a key receptor for TGF‐b signaling) in bone cells by osteocalcin‐Cre resulted in a controversial long bone phenotype: an increase in trabecular bone but a decrease in cortical bone. To address the role of Tgfbr2 in postnatal mandibular development, we first generated a mouse line in which Tgfbr2 was conditionally deleted in early mesenchymal progenitors by crossing Gli1 ‐Cre ERT2 ; Tgfbr2 fl/fl ; and R26R tdTomato (for cell lineage tracing) compound mice (early cKO). This early cKO line was induced at P5 and harvested at P28. Compared to the control littermates, BV/TV and BMD were significantly reduced in both the cortical bone and alveolar bone of the mandible based on uCT analysis (n = 4; p<0.05). Masson trichrome and polarized light images showed a loss of periodontal ligament fibers and bone mass in the early cKO, whereas there was no apparent change in TRAP positive cells in the cKO bone, excluding the impact of osteoclasts on bone phenotypes. The cell lineage tracing data reveals a great reduction in red bone cell numbers in early cKO. Immunostain images revealed a 70% reduction of OSX in the early cKO bone cells (p < 0.001). Immunostain images also displayed a sharp reduction of bone matrix markers such as MEPE and SOST in the cKO, supporting a requirement of Tgfbr2 in the early osteogenesis. Next, we generated a mouse line in which Tgfbr2 was conditionally deleted in osteoblasts by crossing 3.2 Col1 ‐Cre ERT2 ; Tgfbr2 fl/fl ; R26R tdTomato compound mice ( late‐ cKO). Both uCT and histological data showed mild reduction of bone volume in the late cKO compared to the control littermates. The tracing data revealed little change in bone cell number, and immunostain images showed no apparent alternations in OSX or other bone markers. Importantly, in both cKO mice, there is no apparent change in postnatal long bone development, which suggests that TGF‐b signaling plays a more critical role in the neural‐crest derived mandible growth. Based on the above data, we conclude that Tgfbr2 in mandible bone formation is mainly required for early bone progenitor cells, and deletion of Tgfbr2 has little impact on the late bone‐forming cells during postnatal development of alveolar bone.