Inhibition versus activation of canonical Wnt-signaling, to promote chondrogenic differentiation of Mesenchymal Stem Cells. A review.

Fat infiltration within the bone marrow is easily observed in some postmenopausal women. Those fats are mainly derived from bone marrow mesenchymal stem cells (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs significantly contributes to osteoporosis. Icariin is the main extractive of Herba Epimedii which is widely used in traditional Chinese medicine. In this experiment, we investigated the effect of icariin on the bidirectional differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence, western blot, and tissue sections in vitro and in vivo. We found that icariin obviously promotes osteogenesis and inhibits adipogenesis through detecting staining and gene expression. Micro-CT analysis showed that icariin treatment alleviated the loss of cancellous bone of the distal femur in ovariectomized (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot and immunofluorescence showed that icariin regulates the bidirectional differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates that icariin exerts its antiosteoporotic effect by regulating the bidirectional differentiation of BMMSCs through the canonical Wnt signaling pathway.

Download Full-text

Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis

eLife ◽

10.7554/elife.59459 ◽

2021 ◽

Vol 10 ◽

Author(s):

Junjun Jing ◽

Jifan Feng ◽

Jingyuan Li ◽

Hu Zhao ◽

Thach-Vu Ho ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Wnt Signaling ◽

Adult Stem Cells ◽

Cell Types ◽

Tissue Homeostasis ◽

Canonical Wnt Signaling ◽

Multiple Organs ◽

Canonical Wnt

Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs and MSCs have distinct genetic programs and engage in reciprocal signaling cross talk to maintain tissue homeostasis. Specifically, an IGF-WNT signaling cascade is involved in the feedforward from MSCs to TACs. TACs are regulated by tissue-autonomous canonical WNT signaling and can feedback to MSCs and regulate MSC maintenance via Wnt5a/Ror2-mediated non-canonical WNT signaling. Collectively, these findings highlight the importance of coordinated bidirectional signaling interaction between MSCs and TACs in instructing mesenchymal tissue homeostasis, and the mechanisms identified here have important implications for MSC–TAC interaction in other organs.

Download Full-text

Bortezomib induces osteoblast differentiation via Wnt-independent activation of β-catenin/TCF signaling

Blood ◽

10.1182/blood-2008-08-174300 ◽

2009 ◽

Vol 113 (18) ◽

pp. 4319-4330 ◽

Cited By ~ 94

Author(s):

Ya-Wei Qiang ◽

Bo Hu ◽

Yu Chen ◽

Ying Zhong ◽

Bingyin Shi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Wnt Signaling ◽

Nuclear Translocation ◽

Dominant Negative ◽

Calcium Deposition ◽

Canonical Wnt Signaling ◽

Matrix Mineralization ◽

Canonical Wnt

Abstract Inhibition of Wnt/β-catenin/T-cell factor (TCF) signaling induces proliferation of mesenchymal stem cells and/or suppresses their differentiation into osteoblasts (OBs). Osteolysis in multiple myeloma (MM) is related to the suppression of canonical Wnt signaling caused by DKK1, a soluble inhibitor of this pathway secreted by MM cells. Bortezomib (Bzb) can induce OB differentiation in vitro and in vivo and its anti-MM efficacy linked to bone anabolic effects. However, the molecular basis of the action of Bzb on bone is not completely understood. In the present study, we show that Bzb promotes matrix mineralization and calcium deposition by osteoprogenitor cells and primary mesenchymal stem cells via Wnt-independent activation of β-catenin/TCF signaling. Using affinity pull-down assays with immunoblotting and immunofluorescence, we found that Bzb induced stabilization of β-catenin. Nuclear translocation of stabilized β-catenin was associated with β-catenin/TCF transcriptional activity that was independent of the effects of Wnt ligand-receptor-induced signaling or GSK3β activation. Blocking the activation of β-catenin/TCF signaling by dominant negative TCF attenuated Bzb-induced matrix mineralization. These results provide evidence that Bzb induces OB differentiation via Wnt-independent activation of β-catenin/TCF pathway and suggest that proteasome inhibition therapy in MM may function in part by subverting tumor-induced suppression of canonical Wnt signaling in the bone microenvironment.

Download Full-text