Mice Lacking the Calcitonin Receptor Do Not Display Improved Bone Healing

Cells. 2021 Sep 3;10(9):2304. doi: 10.3390/cells10092304.


Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing.

Keywords: bone repair; calcitonin; calcitonin receptor; osteoblasts; osteoclasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • Bone Regeneration / physiology*
  • Bone and Bones / metabolism*
  • Bone and Bones / physiology
  • Cell Differentiation / physiology
  • Female
  • Lysophospholipids / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / metabolism
  • Osteoblasts / physiology
  • Osteoclasts / metabolism
  • Osteoclasts / physiology
  • Receptors, Calcitonin / metabolism*
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Sphingosine-1-Phosphate Receptors / metabolism


  • Lysophospholipids
  • Receptors, Calcitonin
  • Sphingosine-1-Phosphate Receptors
  • sphingosine 1-phosphate
  • Sphingosine