Fang‐Ji‐Huang‐Qi‐Tang Attenuates Degeneration of Early‐Stage KOA Mice Related to Promoting Joint Lymphatic Drainage Function

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the breakdown of articular cartilage, subchondral bone remodeling, and inflammation of the synovium. In this study, we investigated whether Fang-Ji-Huang-Qi-Tang (FJHQT) decoction improved the joint structure of OA or delayed the process of knee joint degeneration in OA mice by promoting lymphatic drain function. The mice were randomly divided into four groups, the sham group, the PBS group, the FJHQT-treated group, and the Mobic-treated group. The mice in each group were tested for lymphatic draining function at 4, 6, 8, and 10 weeks postsurgery (WPS), then sacrificed (N = 10/group). Using a near-infrared indocyanine green (NIR-ICG) lymphatic imaging system, we found that the lymphatic drain function was significantly reduced in the PBS group compared with the sham group. After treatment with the FJHQT decoction, the lymphatic draining function improved at 4 wps and 6 wps. The results of the analysis indicated a strong correlation between lymphatic draining function (ICG clearance) and the degree of joint structural damage (OARSI score). By Alcian blue/orange G (ABOG) staining of the paraffin sections, the FJHQT-treated group exhibited less cartilage destruction and lower OARSI scores. Moreover, the result of immunohistochemical staining (IHC) shows that FJHQT decoction increased the content of type II collagen in knee joints of OA mice at 4 wps and 6 wps. By the double immunofluorescence staining of podoplanin and smooth muscle actin in the paraffin sections, the capillaries and mature lymphatics in the FJHQT group increased at 4 wps. In conclusion, the FJHQT decoction can increase lymphatic vessel number, promote joint lymphatic draining function, and postpone knee osteoarthritis pathologic progression in the early stage of a collagen-induced mouse model. Therefore, the application of sufficient lymphatic drainage in the knee joint may be a new treatment method for knee joint osteoarthritis (KOA).

Exosomes Derived from M2 Macrophages Exert a Therapeutic Effect via Inhibition of the PI3K/AKT/mTOR Pathway in Rats with Knee Osteoarthritic

“…However, with the progress of KOA, the synovial inflammation gradually stabilized, and cartilage destruction became the main pathological manifestation of KOA. In this study, we observed the expression and change of synovial inflammation in the process of KOA from the molecular biology level through animal experiments [ 27 ]. After the intervention of M2-exo, the articular cartilage structure was intact, the chondrocytes were evenly distributed, the tide line was intact, and there were no obvious cartilage defects or cartilage.…”

Effect of human synovial fluid from osteoarthritis patients and healthy individuals on lymphatic contractility

“…Based on historic evidence, the lymphatic system has been proposed to play an important role in the development and progression of OA (Reimann et al, 1989;Wilkinson and Edwards, 1991;Walsh et al, 2012;Shi et al, 2014). Although the involvement of lymphatics has been established for a long time, only recent studies have focused on utilizing the lymphatic system as therapeutic modality for OA (Han et al, 2020).…”

“…Furthermore, blocking lymphangiogenesis with VEGR3 neutralizing antibodies in a mouse model reduced synovial drainage and worsened disease progression (Wang et al, 2019). Given the established implication of the lymphatic system in the disease of OA, there is an increasing interest of studies trying to target lymphatics as a therapeutic modality (Han et al, 2020). Although there is evidence of a correlation between the lymphatic system and OA, its specific role and function is not yet fully explained.…”

Management of osteoarthritis: From drug molecules to nano/micromedicines

“…All these events together with the products of ECM degradation induce an inflammatory response that triggers the OA degenerative cycle, until complete tissue destruction (Goldring & Otero, 2011 ; Lee et al, 2013 ; Loeser et al, 2016 ; Maldonado & Nam, 2013 ; Martin & Buckwalter, 2006 ). Also, they induce an alteration of both structure and function of the lymphatic system (Han et al, 2020 ; Shi et al, 2014 ). Under pathological conditions HA helps to prevent invasion of inflammatory cells into the joint space (Moreland, 2003 ).…”