Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Abstract

Objectives As both adipocytes and osteoblasts originate from the same pool of mesenchymal stem cells, increasing clinical evidence has emerged of the plasticity between the two lineages. For instance, the downregulation of osteoblast differentiation and upregulation of adipogenesis are common features of conditions such as multiple myeloma, obesity and drug-induced bone loss in diabetes mellitus. However, despite in-vitro and in-vivo observations of adipocyte transdifferentiation into osteoblasts, little is known of the underlying mechanisms. Key findings This review summarises the current knowledge of this particular transdifferentiation process whereby the Wnt/b-catenin signalling pathway and Runx2 overexpression have been postulated to play a critical role. Summary Furthermore, due to the possibility of a novel therapy in the treatment of bone conditions, a number of agents with the potential to induce adipo-toosteoblast transdifferentiation have been investigated such as all-trans retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth factor.

Targeting of cancer stem cells by differentiation therapy

“…For orthopedic disorders such as osteoporosis and bone dysplasia, transdifferentiation of myoblasts or adipocytes into osteoblasts also has the potential to provide a novel therapy. 17,24 Many studies have now provided a proof-of-concept for therapeutic transdifferentiation.…”

“…The differentiation of MSCs into preadipocytes during adipogenesis is induced by the action of insulin, dexamethasone, cyclic AMP, and bone morphogenetic protein 4. 24 Transcription factors that contribute to adipocyte differentiation include CCAAT/enhancer binding protein-α (C/EBPα), C/EBPβ, and peroxisome proliferator-activated receptor-γ (PPARγ).…”

“…Activation of such signaling through TLRs and the transcription factor nuclear factor‐κB triggers epigenetic changes such as DNA demethylation and chromatin modification that affect cellular plasticity. For orthopedic disorders such as osteoporosis and bone dysplasia, transdifferentiation of myoblasts or adipocytes into osteoblasts also has the potential to provide a novel therapy 17,24 . Many studies have now provided a proof‐of‐concept for therapeutic transdifferentiation.…”

“…The differentiation fate of a particular lineage is determined by growth factors, ECM proteins, cytokines, and cell‐to‐cell contact, 40,41 with differentiation being executed through the action of various transcription factors (Figure 1). The differentiation of MSCs into preadipocytes during adipogenesis is induced by the action of insulin, dexamethasone, cyclic AMP, and bone morphogenetic protein 4 24 . Transcription factors that contribute to adipocyte differentiation include CCAAT/enhancer binding protein‐α (C/EBPα), C/EBPβ, and peroxisome proliferator‐activated receptor‐γ (PPARγ).…”

Adipocyte-induced transdifferentiation of osteoblasts and its potential role in age-related bone loss

“…Transdifferentiation, also known as lineage reprogramming, is the conversion of one mature somatic cell into another mature somatic cell without going through a pluripotent state [11]. Several in vitro studies using human BMSCs or mature osteoblasts derived from trabecular bone have demonstrated the occurrence of transdifferentiation between osteoblastic and adipocytic phenotypes in response to extrinsic factors [11][12][13][14].…”