Targeted disruption of adenosine kinase in myeloid monocyte cells increases osteoclastogenesis and bone resorption in mice

Int J Mol Med. 2018 Apr;41(4):2177-2184. doi: 10.3892/ijmm.2018.3394. Epub 2018 Jan 17.

Abstract

Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism. Mice were evaluated by means of gross observation and bone histomorphometric analysis. Ex vivo osteoclast differentiation and bone resorption were also examined using genetic deletion and pharmacologic inhibition of ADK in osteoclasts. Compared with control mice, the results of the present study demonstrate that adult mice lacking ADK in the myeloid monocyte cells had reduced body weight and nasoanal length. The results of bone histomorphometric analysis revealed that bone mass was significantly decreased and osteoclastic parameters were increased in the study mice. Furthermore, in vitro cell culture revealed that inhibition of ADK function promoted osteoclast differentiation and bone resorption. Osteoclast‑associated gene expression, including tartrate‑resistant acid phosphatase, nuclear factor of activated T‑cells, cytoplasmic 1, matrix metalloproteinase 9, Cathepsin K and calcitonin receptor, was also significantly increased. These results suggest that mice with ADK deficiency have reduced bone formation due to increased osteoclastogenesis and bone resorption. The present study provides further insight into the mechanism by which ADK serves a key role in bone metabolism.

MeSH terms

  • Adenosine Kinase / genetics*
  • Animals
  • Bone Resorption / genetics*
  • Bone Resorption / pathology
  • Cells, Cultured
  • Gene Deletion*
  • Male
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Monocytes / pathology
  • Osteoclasts / metabolism
  • Osteoclasts / pathology*
  • Osteogenesis

Substances

  • Adenosine Kinase