Purpose: To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). Patients and Methods: Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. Results: IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8. Conclusion: The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain. Trial registration: ChiCTR2100050133; date registered 17 August 2021.
14 February 2021 in Clinical and Translational Medicine
Background: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. Methods: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. Results: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. Conclusions: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.