Osteogenic potency of stem cell-based genetic engineering targeting Wnt3a and Wnt9a

Singhatanadgit, Weerachai; Varodomrujiranon, Manatsanan

doi:10.2478/s11535-011-0079-8

Cited by 1 publication

(2 citation statements)

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“…Interestingly, Wnt9a expression was shown to be downregulated during the differentiation of precursor cells into mature osteoblasts, and knockdown of Wnt9a in osteoblasts increased expression of ALP, runx2, a key transcription factor for osteoblast differentiation, and osteocalcin, a late marker of osteoblast differentiation [32, 33]. In addition, knockdown of Wnt9a in osteoblasts increased their degree of mineralization [33], indicating that Wnt9a is an inhibitor of osteoblast differentiation. PCR array analysis revealed that the Wnt receptors Fzd1, 2, 3, 4, 5, 6, 7, and Lrp5 and Lrp6 were expressed in WT BMSCs cultured for 2 days in osteogenic differentiation medium.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings show that lack of ANK function results in decreased expression of several Wnt ligands, Wnt receptors and Wnt signaling proteins in BMSCs when cultured in osteogenic differentiation medium that have been shown to stimulate Wnt/β-catenin signaling in these cells and ultimately osteogenesis [14]. In contrast, Wnt9a, a Wnt ligand that has been shown to inhibit osteogenesis was increased in ank/ank BMSCs [33]. These findings suggest that the increased expression of ANK during early osteogenesis is a key mediator of stimulating the expression of Wnt ligands and receptors, including Lrp5 and Lrp6, key co-receptors for the activation of Wnt/β-catenin signaling, and Wnt signaling proteins that are required for osteogenic fate decision of adult mesenchymal stem cells [15].…”

Section: Discussionmentioning

confidence: 99%

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

Minashima

Quirno

Lee

et al. 2017

Bone

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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.

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Section: Resultsmentioning

confidence: 99%