Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Wang, Lijun; You, Xiuling; Lotinun, Sutada; Zhang, Lingli; Wu, Nan; Zou, Weiguo

doi:10.1038/s41467-019-14146-6

Cited by 296 publications

(358 citation statements)

References 53 publications

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“…As an essential factor for osteoclastogenesis, RANKL is widely expressed by a variety of cells types within the bone marrow (24). (6,25). And osteocytes are an essential source of RANKL for cancellous bone remodeling in adult mice but not younger mice (6,24).…”

Section: Discussionmentioning

confidence: 99%

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RANKL from Bone Marrow Adipose Lineage Cells Promotes Osteoclast Formation and Bone Loss

Zhi

Yan

et al. 2020

Preprint

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Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation. The cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Bone marrow (BM) adipocytes derived from bone marrow mesenchymal stromal cells (BMSCs) express RANKL. Here we demonstrated that the AdipoqCre could target bone marrow adipocytes. We crossed the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipocytes. Conditional deletion of RANKL increased cancellous bone mass in the long bones of growing and adult mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but did not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre; ranklfl/fl mice exhibited resistance to estrogen deficiency and rosiglitazone (ROS) induced trabecular bone loss but showed bone loss induced by unloading. BM adipocytes therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling.

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Section: Discussionmentioning

confidence: 99%

“…Osteocytes sense mechanical loading and secrete RANKL to control osteoclast formation and bone remodeling in adult mice and unloading-induced bone loss (6,25).…”

Section: Discussionmentioning

confidence: 99%

RANKL from Bone Marrow Adipose Lineage Cells Promotes Osteoclast Formation and Bone Loss

Zhi

Yan

et al. 2020

Preprint

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“…Among them are type II and IX collagens, whose deposition in the extracellular matrix in turn regulate bone resorption by osteoclasts [156].…”

Section: Yap and Taz As Regulators Of Osteogenesismentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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“…Mouse MSCs The increased expression of YAP1 in the nucleus promotes the osteogenesis of MSCs, inhibits their adipogenic differentiation, and leads to dedifferentiation of chondrocytes Bian et al, 2016 Mouse osteoblast The regulation of OB by YAP1/TAZ is closely associated with the developmental stage of individuals and the differentiation state of cells Xiong et al, 2018 Mouse osteoblast Piezo1 in osteoblasts promotes the expression of COL2α1 and COL9α2 in osteoblast cell lines through YAP1 Wang et al, 2020 Mouse osteoclast YAP1 is an essential regulator for osteoclast differentiation and activity Zhao et al, 2018 the intra-articular injection of verteporfin, a selective inhibitor of YAP1, can significantly maintain cartilage homeostasis in a mouse OA model and that a sustained-release system consisting of chitosan microspheres and verteporfin has significant anti-OA effects (Zhang et al, 2020). Another YAP1 activity inhibitor, dasatinib, can also perform a similar function (Nie et al, 2019).…”

Section: Guo Et Al 2018mentioning

confidence: 99%

Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

Xie

Xiao

Tang

et al. 2020

Front. Cell Dev. Biol.

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The Hippo/yes-associated protein 1 signaling pathway is an evolutionarily conserved signaling pathway. This signaling pathway is primarily involved in the regulation of stem cell self-renewal, organ size and tissue regeneration by regulating cell proliferation, differentiation and apoptosis. It plays an important role in embryonic development and tissue organ formation. Yes-associated protein 1 (YAP1) is a key transcription factor in the Hippo signaling pathway and is negatively regulated by this pathway. Changes in YAP1 expression levels affect the occurrence and development of a variety of tumors, but the specific mechanism associated with this phenomenon has not been thoroughly studied. Recently, several studies have described the role of YAP1 in osteoarthritis (OA). Indeed, YAP1 is involved in orthopedic degenerative diseases such as osteoporosis (OP) in addition to OA. In this review, we will summarize the significance of YAP1 in orthopedic degenerative diseases and discuss the potential of the targeted modulation of YAP1 for the treatment of these diseases.

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Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Cited by 296 publications

References 53 publications

RANKL from Bone Marrow Adipose Lineage Cells Promotes Osteoclast Formation and Bone Loss

RANKL from Bone Marrow Adipose Lineage Cells Promotes Osteoclast Formation and Bone Loss

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

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