Table 2.
YAP Involves the Regulation of Pathophysiological Process in OA
| Signaling | Cell types | Main Results | Reference |
|---|---|---|---|
| YAP–FOXD1 signaling | Human mesenchymal stem cell (hMSC) | Overexpression of YAP or FOXD1 reduces the number of senescent cells, inhibits articular inflammation and cartilage erosion and ameliorates the pathological symptoms in OA. | Lina Fu et al86 |
| YAP/TAZ -NF-κB signaling | HEK293A, HEK293T, HeLa cells | YAP is both necessary and sufficient for the maintenance of cartilage homeostasis in osteoarthritis, Treatment of IL-1β or TNF-α showed increased expression of matrix degrading enzymes and ECM consistent with the result of promoting YAP degradation. Interaction of YAP/TAZ and NF-κB signaling pathway regulates the cartilage metabolism in OA. | Yujie Deng, et al88 |
| / | Chondrocytes | YAP overexpression resulted in increased expression of catabolic genes, suppression of YAP inhibited catabolic genes expression and chondrocytes apoptosis. Intra-articular injection of YAP siRNA ameliorated OA pathological progress in mice. | Yong Gong, et al79 |
| Wnt-YAP signaling | C3H10T1/2 cells, HEK293 cells, C28/I2 cells | Inhibiting the expression of YAP improved the cartilage integrity and relieved pain in OA, the mechanical stress and inflammation factors could activate the Wnt5a and ROR2, induced the nuclear localization of YAP and activity of catabolism. | Anne-Sophie Thorup, et al89 |
| Wnt-YAP signaling | Chondrocytes | The exosomes derived from synovial mesenchymal stem cells could activate the YAP to localize in the cell nucleus via the Wnt5a and Wnt5b, finally resulted in the proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion through Wnt-YAP signaling pathway. | Shi-Cong Tao, et al82 |
| / | Chondrocytes | Increased YAP expression and nuclear localization resulted chondrocytes presented an OA phenotype mainly include the decreasing expression of Col2a1 and Sox9, increased extracellular matrix stiffness and degeneration of articular cartilage confirmed by the higher OARSI histological scores. Deletion of YAP or pharmacological inhibited the expression of the YAP showed an opposite result. | Xianzhu Zhang, et al80 |
| / | ATDC5 cells | Overexpression of YAP1 significantly suppressed ATDC5 chondrogenic cell proliferation and decreased the expression of differentiation-related genes including Runx2, osteocalcin, and collagen I, and elevated cell apoptosis, whereas these cellular processes were reversed by knockdown of YAP1. The mechanism of YAP regulated the progress of OA mainly through interacting with beclin-1 and promoting the apoptosis of ATDC5 cells, suggesting that YAP1 functions as a negative regulator of autophagy. | Qiang Zhang, et al83 |
| Hippo-YAP signaling | Fibroblast-like synoviocytes | Resolvin D1 inhibited OA- fibroblast-like synoviocytes proliferation and reduced MMP-13 and IL-1β secretion. Furthermore, resolvin D1 inhibits the proliferation of OA-fibroblast-like synoviocytes by arresting the cell cycle via the Hippo-YAP signaling pathway and promoted YAP phosphorylation. | Siwei Su, et al90 |
| YAP-ERK signaling | Chondrocytes | YAP and ERK activation in response to mechanical strain was time and magnitude dependent. Activated YAP and ERK could induce cell cycle progression and promote cell proliferation by up-regulating the expression of cycle-related genes. | Kaixiang Yang, et al91 |
| / | Chondrocytes | YAP1 was highly expressed in OA chondrocytes. MiR-582-3p inhibited chondrocyte apoptosis, reduced the proinflammatory cytokine production and suppressed extracellular matrix degradation via regulation of the expression of YAP1 in chondrocytes. | Jun He, et al92 |
| YAP-BMP signaling | Human mesenchymal stem cells | Overexpression of YAP inhibited chondrogenic differentiation, YAP is a negative regulator of chondrogenic differentiation in human mesenchymal stem cells. High expression of YAP suppressed chondrogenic differentiation and proliferation of stem cells by inhibiting BMP signaling pathway. | Alexandra Karystinou, et al93 |
| RhoA/YAP signaling | Chondrocytes | Mechano growth factor could inhibit chondrocytes apoptosis and inflammation, but have no effect on chondrocyte proliferation and differentiation activity. Mechano growth factor promoted chondrocytes migration which was accompanied with YAP activation and nucleus translocation via the activation of RhoA-YAP signaling pathway. | Xingzhi Jing, et al94 |
| Hippo- YAP signaling | ATDC cells | The silencing of SETD7 inhibited the Hippo signaling pathway in ATDC5, decreased YAP phosphorylation and increased the levels of YAP and hypoxia inducible factor-1α (HIF-1α) in the nucleus. YAP combined with HIF-1α to form a complex that promoted the expression of genes involved in chondrogenic differentiation and the glycolytic pathway. | Maoquan Li, et al95 |
| / | Chondrocytes | Cyclic mechanical stress promoted HIF-1α and YAP expression in a magnitude dependent manner. Activation of YAP promoted HIF-1α stabilization and expression in chondrocytes. | Xingzhi Jing, et al96 |
| Hippo- YAP signaling | ATDC5 cells | Fluoride exposure could lead to the decrease of YAP in cytoplasm of chondrocytes accompanied by the increase of YAP location in the nucleus, finally resulted in the decrease of type II collagen and increase repression of MMP-13, and the degeneration and injury of articular cartilage. | Fang-fang Yu, et al97 |
| Src/Hippo-YAP Signaling | Mesenchymal stem cells | Dasatinib promoted chondrogenic differentiation and inhibited osteogenic differentiation of MSCs. Dasatinib inhibited the expression of YAP and TAZ and the phosphorylation of Src. Inhibition of the Hippo pathway dramatically suppressed the serine phosphorylation of YAP and chondrogenic differentiation of MSCs. Dasatinib promoted chondrogenic differentiation of MSCs via the Src/Hippo-YAP signaling pathway. | Ping Nie, et al98 |
| HIF-1α/YAP signaling | Chondrocytes | Hypoxia leads to OA phenotype in chondrocytes through HIF-1α-YAP pathway accompanied by the increased nuclear location of YAP, while inhibited the expression of HIF-1α decreased the activity and expression of YAP and Sox9 under hypoxia. | Hao Li, et al99 |
| Hippo- YAP signaling | Chondrocytes | The response of chondrocytes to substrate stiffness is associated with changes in YAP localization. Down-regulation of YAP expression helps maintain chondrocyte phenotype and inhibit chondrocyte proliferation. | Weiliang Zhong, et al85 |
| YAP-Wnt/β-catenin signaling | ATDC5 cells | Overexpression of YAP1 could promote chondrocyte proliferation but inhibit chondrocyte differentiation, which is contrary to the result of YAP1 knockout. YAP1 attenuated chondrogenesis and hypertrophic differentiation of ATDC5 cells via activating the Wnt/β-catenin signaling pathway. | Beining Yang, et al84 |
| / | Chondrocytes | YAP1 differentially regulates chondrocyte differentiation in skeletal development and bone repair. YAP1 regulated Sox6 expression to promote chondrocyte proliferation, inhibited Col10a1 expression through interaction with Runx2 during chondrocyte maturation. | Yujie Deng, et al73 |
| Autotaxin–YAP Signaling | Bone marrow mesenchymal stem cells | Exosomes derived from mesenchymal stem cells regulate the expression of YAP in chondrocytes, and the increased expression and nuclear localization of YAP in chondrocytes played an important role in promoting cell proliferation and cartilage matrix synthesis, inhibiting inflammatory response and anti-apoptosis through the YAP/TAZ signaling pathway. | Yingnan Wang, et al16 |
| / | Mesenchymal stem cells | Declined YAP activity inhibited the proliferation, migration and osteogenic of mesenchymal stem cells, accompanied by the down regulation of osteogenic and upregulation of fibroblast genes. | Chanchao Lorthongpanich, et al87 |