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.
Osteoarthritis (OA) is closely related to aging, and autophagy is implicated in the retardation of aging. Activated synoviocytes play important roles in OA; the synoviocytes could produce osteopontin (OPN) and its main receptors CD44 and integrin, which are all involved in OA. The purpose of this study is to investigate whether OPN has an effect on autophagy in osteoarthritic synoviocytes. We cultured human OA fibroblast-like synoviocytes (FLS) and treated them with rhOPN and antibodies against CD44 and CD51/61 (αvβ3 integrin) or isotype IgG to block the interaction between receptors and ligands. Infection with lentivirus mRFP-GFP-LC3, laser confocal imaging and Western blotting were used to determine changes in the expression of autophagy markers, and cell proliferation of FLS was assessed with a CCK-8 assay. Our results showed the expression level of autophagy marker protein LC3 II and the mRFP-GFP-LC3 puncta were significantly decreased after treatment with rhOPN when compared with the control group, when the FLS were incubated with antibodies against CD44 or CD51/61 (αvβ3 integrin) or with control isotype IgG for 1 h, followed by rhOPN treatment for 48 h, rhOPN could suppress the relative expression of LC3 II and Beclin1 via integrin and CD44 in the FLS, CCK-8 assay also showed that rhOPN significantly increased the cell proliferation and viability of FLS. OPN could inhibit autophagy via CD44 and αvβ3 integrin and promote the proliferation of FLS, playing an important role in OA synovitis.
Hydatid disease is an infectious disease caused by echinococcus granulosus which mainly caused liver and lungs damaged in humans. Bone involvement is rare and accounts for only 0.5%-4% in hydatid disease, spine is more prone to be infected with a proportion of 50% in musculoskeletal tissue. We present a case of spinal hydatidosis in a 47‑year‑old male presenting with low back pain radiating to the legs, progressive weakness and hypaesthesia in the lower limbs accompanied with difficulty walking. Computed tomography (CT) images showed a spinal hydatid cyst in lumbar vertebra2 and caused bone destruction of the vertebral body and lamina. Magnetic resonance imaging (MRI) images showed hyperintense cystic components on lumbar vertebra2 with the appearance of a lobulated, multiocular, septated cystic mass and compressing of the spinal cord at segments lumbar vertebra1-2. The patient underwent subtotal vertebral resection to completely remove the damaged vertebral and paravertebral cysts, and histopathological examination showed the characteristic features of hydatid cysts. The patient received antiparasitic drugs treatment post-operation. The surgical removement combined with antiviral drugs is an effective way to treat spinal hydatidosis.
Background Hydatid disease is an infectious disease caused by echinococcus that causes liver and lung damage in humans. Bone involvement is rare and accounts for only 0.5%-4% of hydatid diseases; the spine is more prone to be infected with a proportion of 50% in musculoskeletal tissue. Missed hydatid cysts may lead to serious consequence, it is necessary to diagnosis and treatment of hydatid cysts at early stage. Case presentation We present a case of a 47-year-old Han Chinese male diagnosed with spinal hydatidosis. The patient lived in pasturing areas accompanied by symptoms of low back pain radiating to the legs, progressive weakness, and hypoesthesia in the lower limbs accompanied by difficulty walking. Computed tomography (CT) images showed a spinal hydatid cyst in the lumbar vertebra2 (L2) that caused bone destruction in the vertebral body and lamina. Magnetic resonance imaging (MRI) images showed hyperintense cystic components on L2 with the appearance of a lobulated, multiocular, septate cystic mass and compression of the spinal cord at the segments of L2. The patient underwent subtotal vertebral resection to completely remove the damaged vertebral and paravertebral cysts, and histopathological examination revealed the characteristic features of hydatid cysts. The patient received a postoperative antiparasitic drug treatment and finally achieved a successful treatment. Conclusions Spinal hydatidosis is a rare infectious disease. It should be considered as an important differential diagnosis for patients accompanying by spinal bone destruction with animal contact history. Surgical removal combined with antiviral drugs is an effective way to treat spinal hydatidosis. In addition, long term follow-up is mandatory for avoiding its recurrence.