The role of the progressive ankylosis protein (ANK) in adipogenic/osteogenic fate decision of precursor cells

Abstract

The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates. Wnt signaling pathway PCR array analysis revealed that Wnt ligands, Wnt receptors and Wnt signaling proteins that stimulate osteoblast differentiation were expressed at markedly lower levels in ank/ank BMSCs than in WT BMSCs. Lack of ANK function also resulted in impaired bone fracture healing, as indicated by a smaller callus formed and delayed bone formation in the callus site. Whereas 5 weeks after fracture, the fractured bone in WT mice was further remodeled and restored to original shape, the fractured bone in ank/ank mice was not fully restored and remodeled to original shape. In conclusion, our study provides evidence that ANK plays a critical role in the adipogenic/osteogenic fate decision of adult mesenchymal precursor cells. ANK functions in precursor cells are required for osteogenic differentiation of these cells during adult bone homeostasis and repair, whereas lack of ANK functions favors adipogenic differentiation.

Ankylosis progressive homolog upregulation inhibits cell viability and mineralization during fibroblast ossification by regulating the Wnt/β‑catenin signaling pathway

“…This result was consistent with a previous study, which demonstrated that anK was negatively associated with ALP expression levels in bone marrow stromal cells (38). OCN is a marker unique to osteoblasts and a late marker of osteoblast differentiation (38,39). In the present study, the expression levels of ocn and runx2 were downregulated in ANKH-overexpressing cells.…”

“…In the present study, ANKH overexpression downregulated ALP expression levels in fibroblasts from patients with AS. This result was consistent with a previous study, which demonstrated that anK was negatively associated with ALP expression levels in bone marrow stromal cells (38). OCN is a marker unique to osteoblasts and a late marker of osteoblast differentiation (38,39).…”

β-TCP from 3D-printed composite scaffolds acts as an effective phosphate source during osteogenic differentiation of human mesenchymal stromal cells

“…Progressive ankylosis protein homolog (ANK), encoded by the ANKH gene, is highly expressed in osteoblasts ( Szeri et al, 2020 ). It is involved in the osteogenic fate decision of adult mesenchymal precursor cells and its absence has been shown to favor adipogenesis ( Minashima et al, 2017 ). ANKH is used as a osteogenic marker of BM-MSCs due to its association with ALP ( Granchi et al, 2010 ).…”

Spontaneous intake of essential oils after a negative postnatal experience has long-term effects on blood transcriptome in chickens

“…Besides oxidative stress, a number of the differentially regulated genes in males have interesting properties, such as the up-regulated genes related to bone metabolism: ANKH has a role in osteogenic differentiation of bone marrow stromal cells and is a vascular calcification inhibitor 27,28 and SOST is a negative regulator of bone growth 29,30 . Moreover, the transcription factor TEAD1 over-represented in the Delayed males supports an effect of delayed placement on bone metabolism by regulating organ size and skeletal muscle mass 31 .…”