Immunohistological identification of receptor activator of NF-kappaB ligand (RANKL) in human, ovine and bovine bone tissues.

Receptor activator of NF-kappaB ligand (RANKL, also called ODF/TRANCE/OPGL) is the final factor of osteoclast differentiation. Osteoclastogenesis may be determined by its receptor RANK and the relative ratio of RANKL to its decoy receptor osteoprotegerin (OPG), and alterations in this ratio may be a major cause of bone loss in many metabolic and immunologic disorders. In order to get a better insight into this complex regulatory system, this study aimed to determine where RANKL protein is located in bone tissues. RANKL was stained immunohistochemically in ex vivo human, ovine and bovine bone tissue. RANKL was observed labelled in the membrane of osteoblasts, osteocytes and osteoclasts and their surrounding matrix. In cartilage, which was used as a negative tissue control, chondrocytes were not stained. The presence of RANKL protein in the membrane of osteoblasts and also the secretion of RANKL by osteoclasts has been hypothesised in earlier studies. In this study, RANKL protein was shown histologically for the first time in the membrane and in the long processes of osteocytes. The result strongly suggests the crucial involvement of osteocytes in terms of orchestrating bone remodelling by influencing differentiation and activation of osteoclasts.