The Hippo-YAP Signaling Pathway in Osteoarthritis and Rheumatoid Arthritis.

Arthritis is the most prevalent joint disease and is characterized by articular cartilage degradation, synovial inflammation, and changes in periarticular and subchondral bone. Recent studies have reported that Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) have significant effects on the proliferation, migration, and survival of chondrocytes and fibroblast-like synovial cells (FLSs). YAP/TAZ signaling pathway, as well as the related Hippo-YAP signaling pathway, are responsible for the condition of cells and articular cartilage in joints. They are tightly regulated to maintain metabolism in chondrocytes and FLSs because abnormal expression may result in cartilage damage. However, the roles and mechanisms of the Hippo-YAP pathway in arthritis remain largely unknown. This review summarizes the roles and key functions of YAP/TAZ and the Hippo-YAP signaling pathway in FLSs and chondrocytes for the induction of proliferation, migration, survival, and differentiation in rheumatoid arthritis (RA) and osteoarthritis (OA) research. We also discuss the therapeutic strategies involving YAP/TAZ and the related Hippo-YAP signaling pathway involved in OA.

Osteopontin, a bridge links osteoarthritis and osteoporosis.

Osteoarthritis (OA) is the most prevalent joint disease characterized by degradation of articular cartilage, inflammation, and changes in periarticular and subchondral bone of joints. Osteoporosis (OP) is another systemic skeletal disease characterized by low bone mass and bone mineral density (BMD) accompanied by microarchitectural deterioration in bone tissue and increased bone fragility and fracture risk. Both OA and OP are mainly affected on the elderly people. Recent studies have shown that osteopontin (OPN) plays a vital role in bone metabolism and homeostasis. OPN involves these biological activities through participating in the proliferation, migration, differentiation, and adhesion of several bone-related cells, including chondrocytes, synoviocytes, osteoclasts, osteoblasts, and marrow mesenchymal stem cells (MSCs). OPN has been demonstrated to be closely related to the occurrence and development of many bone-related diseases, such as OA and OP. This review summarizes the role of OPN in regulating inflammation activity and bone metabolism in OA and OP. Furthermore, some drugs that targeted OPN to treat OA and OP are also summarized in the review. However, the complex mechanism of OPN in regulating OA and OP is not fully elucidated, which drives us to explore the depth effect of OPN on these two bone diseases.

OPN inhibits autophagy through CD44, integrin and the MAPK pathway in osteoarthritic chondrocytes.

Background: To investigate whether osteopontin (OPN) affects autophagy in human osteoarthritic chondrocytes and determine the roles of CD44, αvß3 integrin and the Mitogen-activated protein kinase (MAPK) pathway in this progress. Methods: First, we compared the autophagy levels in the human osteoarthritis (OA) and normal cartilage, then, we cultured human OA chondrocytes in vitro and treated cells with recombinant human OPN (rhOPN) to determine autophagy changes. Next, the anti-CD44 and anti-CD51/61 monoclonal antibodies (Abs) or isotype IgG were used to determine the possible role of CD44 and αvß3 integrin; subsequently, an inhibitor of the ERK MAPK pathway was used to investigate the role of ERK MAPK. Western blotting was used to measure the Beclin1, LC3 II and MAPK proteins expressions, mRFP-GFP-LC3 confocal imaging and transmission electron microscopy were also used to detect the autophagy levels. Cell Counting Kit-8 (CCK-8) was used to assay the proliferation and activity of chondrocytes. Results: The LC3 protein was greatly decreased in OA cartilage compared to normal cartilage, and OPN suppressed the autophagy activity in chondrocytes in vitro. Blocking experiments with anti-CD44 and anti-CD51/61 Abs indicated that OPN could suppress the expression of LC3II and Beclin1 through αvß3 integrin and CD44. Our results also indicated that the ratio of p-ERK/ERK but not p-P38/P38 and p-JNK/JNK was increased after the rhOPN treatment. The ERK inhibitor inhibited the activity of OPN in the suppression of autophagy, and the CCK-8 results showed that rhOPN could promote chondrocyte proliferation. Conclusion: OPN inhibited chondrocyte autophagy through CD44 and αvß3 integrin receptors and via the ERK MAPK signaling pathway.