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Related Experiment Video

Updated: Mar 1, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Serum CTX levels and histomorphometric analysis in Src versus RANKL knockout mice.

Sunao Takeshita1, Toshio Fumoto2, Masako Ito3

  • 1Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan. sunao@ncgg.go.jp.

Journal of Bone and Mineral Metabolism
|June 8, 2017
PubMed
Summary

Src knockout mice show impaired osteoclast function and osteocyte deficiency, unlike RANKL knockout mice which lack osteoclasts and osteoblasts. Src plays a critical role in osteoclast bone resorption and osteocyte survival.

Keywords:
OsteoblastOsteoclastOsteocyteOsteopetrosis

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Area of Science:

  • Bone biology
  • Skeletal development
  • Cell signaling

Background:

  • Osteopetrosis is characterized by increased bone mass and density.
  • Osteoclasts and osteoblasts are key cells in bone remodeling.
  • Src kinase and RANKL signaling are crucial for osteoclast differentiation and function.

Purpose of the Study:

  • To investigate the distinct roles of Src and RANKL in bone remodeling.
  • To compare the bone phenotypes of Src knockout (KO) and RANKL KO mice.
  • To elucidate the function of Src in osteoclast activity and osteocyte survival.

Main Methods:

  • Micro-computed tomography (micro-CT) for 3D bone volume analysis.
  • Histomorphometry to assess eroded and osteoid surfaces.
  • Analysis of osteoclast and osteoblast numbers and function in vivo and in vitro.

Main Results:

  • Both Src KO and RANKL KO mice exhibit osteopetrosis.
  • Src KO mice show normal serum CTX but reduced bone resorption markers (ES/BS, OS/BS) compared to WT.
  • RANKL KO mice lack osteoclasts and osteoblasts, while Src KO mice have increased osteoclasts but decreased osteoblasts and osteocytes.

Conclusions:

  • Src, but not RANKL, is essential for normal osteoclast bone-resorbing function in vivo.
  • Src plays a significant role in osteoclast and osteoblast regulation.
  • Both RANKL and Src may have unrecognized roles in osteocyte survival.