BoneKEy Reports | BoneKEy Watch
Osteocytes and chondrocytes embedded in bone matrix control bone remodelling
DOI:10.1038/bonekey.2012.9
Osteocytes embedded in the bone matrix resorb the bone made by osteoblasts and chondrocytes. It is known that the cytokine receptor activator of nuclear factor-κB ligand (RANKL) is required for osteocyte formation but, until now, it was thought that RANKL was supplied by osteoblasts and their progenitors even though the exact cell type involved had not been identified.
Two studies published consecutively in Nature Medicine reveal that mineralised cartilage resorption and bone modelling is actually under the control of RANKL expressed by chondrocytes and osteocytes embedded within the bone matrix.
Xiong et al. generated transgenic mice in which RANKL could be conditionally deleted and crossed them with mice that produced osteoblasts and chondrocytes at different stages of differentiation. Analysis of the progeny demonstrated that hypertrophic chondrocytes, which form an integral part of the mineralised cartilage, provide the RANKL necessary for bone growth. Osteocytes within the same matrix respond to mechanical stress and produce the RANKL essential for bone remodelling.
Nakashima et al. determined the level of gene expression of Tnfsf1 1 (which codes for RANKL) in osteoblasts and osteocytes. They used a high-purity isolation method to show that Tnfsf1 1 mRNA expression was more than ten times higher in osteocytes compared to osteoblasts.
Editor's comment: These two seminal papers highlight that osteocytes produce the RANKL required for bone remodelling. The discovery of this unexpected network among cells in the mineralised matrix could reveal new therapeutic targets.
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