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).
Highlights
Osteoarthritis (OA), characterized by a progressive loss of cartilage and subchondral bone, is a degenerative joint disease leading to disability in old people [1]. e treatment of OA is still dominated by nonsteroidal anti-inflammatories; the long-term use of nonsteroidal antiinflammatories usually causes severe gastrointestinal side effects, especially in the elderly [2, 3]
Using near-infrared indocyanine green (NIR-ICG) lymphatic imaging system, we found no significant change in the function of lymphatic drainage in the sham group at 4 weeks (72.485 ± 5.384%) and 6 weeks (72.005 ± 7.901%)
ICG clearance of OA knee joint at 4 weeks (52.597 ± 6.487%) and 6 weeks (41.851 ± 5.509%) was significantly reduced compared with the sham group (Figure 1(a)) while lymphatic drainage function improved at 4 weeks (61.31 ± 9.20%) and 6 weeks (54.537 ± 12.257%) after treatment with FJHQT decoction (Figure 1(a)). e difference was statistically significant (P < 0.05, Figure 1(b))
Summary
Osteoarthritis (OA), characterized by a progressive loss of cartilage and subchondral bone, is a degenerative joint disease leading to disability in old people [1]. e treatment of OA is still dominated by nonsteroidal anti-inflammatories; the long-term use of nonsteroidal antiinflammatories usually causes severe gastrointestinal side effects, especially in the elderly [2, 3]. Osteoarthritis (OA), characterized by a progressive loss of cartilage and subchondral bone, is a degenerative joint disease leading to disability in old people [1]. Previous studies have shown that the function of lymphatic drainage plays an important role in the occurrence and development of osteoarthritis. Ese results have proven that there were abnormal changes in the structure and function of the lymphatic vascular system in the OA joint. Lymphatic vessel formation is a compensatory response to joint inflammation, which may drain inflammatory cytokines away from the OA joint, such as TNFalpha that could increase MMP-13 gene expression by activating ERK, p38, in addition to MAP kinases, and AP-1 and NF-kappa B transcription factors. Erefore, the lymphatic vascular system plays a critical role in the OA pathologic process. Traditional Chinese medicine has been used to treat Chinese patients, including articular disease cases. e FJHQT decoction, invented by the ancient Chinese medical doctor Zhongjing Zhang, is a classic formula that has the function of clearing the dampness and congestion in the joint
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