Chemokine ligand 28 (CCL28) negatively regulates trabecular bone mass by suppressing osteoblast and osteoclast activities

J Bone Miner Metab. 2021 Jul;39(4):558-571. doi: 10.1007/s00774-021-01210-9. Epub 2021 Mar 15.


Introduction: Bone metabolism imbalances cause bone metabolism diseases, like osteoporosis, through aging. Although some chemokines are known to be involved in bone mass regulation, many have not been investigated. Thus, the present study aimed to investigate the role of chemokine ligand 28 (CCL28) on bone metabolism.

Materials and methods: To investigate the role of CCL28 on bone metabolism, 10-week-old male wild-type and Ccl28 knockout (Ccl28 KO) mice were analyzed. Microcomputed tomography analysis and bone tissue morphometry were used to investigate the effect of Ccl28 deficiency on the bone. CCL28 localization in bone tissue was assumed by immunohistochemistry. Osteoblast and osteoclast markers were evaluated by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction. Finally, in vitro experiments using MC3T3-E1 and bone marrow macrophages revealed the direct effect of CCL28 on osteoblast and osteoclast.

Results: This study showed that Ccl28 deficiency significantly increased bone mass and the number of mature osteoblasts. Immunoreactivity for CCL28 was observed in osteoblasts and osteoclasts on bone tissue. Additionally, Ccl28 deficiency promoted osteoblast and osteoclast maturation. Moreover, CCL28 treatment decreased osteoblast and osteoclast activities but did not affect differentiation.

Conclusion: In summary, this study indicated that CCL28 is one of the negative regulators of bone mass by suppressing osteoblast and osteoclast activities. These results provide important insights into bone immunology and the selection of new osteoporosis treatments.

Keywords: Bone metabolism; Chemokine ligand 28; Osteoblast; Osteoclast.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Bone Density
  • Cancellous Bone / anatomy & histology*
  • Cancellous Bone / metabolism
  • Chemokines, CC / deficiency
  • Chemokines, CC / metabolism*
  • Insulin-Like Growth Factor I / metabolism
  • Ligands
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • Osteogenesis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Tibia / anatomy & histology


  • Biomarkers
  • Ccl28 protein, mouse
  • Chemokines, CC
  • Ligands
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt