Macrophage Colony-Stimulating Factor (MCSF) and Receptor Activator of NF₭B Ligand (RANKL) in Osteoclastogenesis

Introduction: Osteoclasts are defined as bone-resorbing cells which have an important function in skeletal development as well as in bone remodelling in the adult stage. Two significant cytokines stimulate the differentiation of osteoclasts from cells of the monocyte/macrophage; the monocyte/macrophage colony-stimulating factor (M-CSF) and receptor activation of NF-κB ligand (RANKL). For osteoclast precursors to proliferate, MCSF needs to bind to its receptor c-Fms which activates the signalling pathway required. Furthermore, RANKL which is the elementary differentiation factor of osteoclast stimulates the process through the gene expression control by activating its receptor.

Aims: This study aims to demonstrate osteoclastogenesis using RAW264.7 line cell in vitro and identify the alterations in gene expression of the progenitor cells that typify osteoclast cells.

Methodology: The study was conducted using hematopoietic precursor cells to examine the cellular differentiation into osteoclast under the control of RANKL. Furthermore, microarrays were used to accurately analyze the expression of the genes of interest by exhibiting the gene expressions changes and expected regulations of osteoclasts marker genes such as Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), Tartrate-resistant acid phosphate (TRAP) and c-FMS.

Results: We have identified that the upregulation of TRAP mRNA expression indicated the differentiation of osteoclast cells in the progenitor cells were induced by RANKL.

Conclusion: The presence of Macrophage Colony-Stimulating Factor (MCSF) stimulates the differentiation of osteoclast progenitors into osteoclasts in the presence of RANKL.