Abstract
BackgroundArticular cartilage degeneration plays a key role in the pathogenesis of osteoarthritis (OA). Bushenhuoxue formula (BSHXF) has been widely used in the treatment of OA in clinics. However, the molecular mechanisms responsible for the chondroprotective effect of BSHXF remain to be elucidated. The purpose of this study was to explore the effects of BSHXF on OA mice model.MethodsIn this study, we investigated the effects of BSHXF on destabilization of the medial meniscus (DMM)-induced chondrocyte degradation in OA mice model. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histology, histomorphometry, TUNEL, OARSI scoring, micro-CT and immunohistochemistry for COL2, TGFBR2, pSMAD2 and MMP13. Additionally, we also evaluated the effects of BSHXF on Mmp13 mRNA and protein expression in chondrogenic ATDC5 cells through real-time PCR and Western blot respectively. Moreover, we investigated the chondroprotective effect of BSHXF on mice with Tgfbr2 conditional knockout (Tgfbr2Col2ER mice) in chondrocyte, including the relative experiments mentioned above. We transfected Tgfbr2 siRNA in ATDC5 to further evaluate the changes of Mmp13 mRNA and protein expression followed by BSHXF treatment.ResultsAmelioration of cartilage degradation and chondrocyte apoptosis were observed in DMM-induced mice, with increases in cartilage area and thickness, proteoglycan matrix, COL2 content and decreases in OARSI score at 12 weeks post surgery. Moreover, the elevated TGFBR2 and pSMAD2, and reduced MMP13 positive cells were also revealed in DMM-induced mice treated with BSHXF. Besides, decreased Mmp13 mRNA and protein expression were observed inchondrogenic ATDC5 cells culture in serum containing BSHXF. As expected, Tgfbr2Col2ER mice exhibited significant OA-like phenotype. Interestingly, obvious improvement in articular cartilage structure was still observed in Tgfbr2Col2ER mice after BSHXF treatment via up-regulated pSMAD2 and down-regulated MMP13 expressional levels in articular cartilage.ConclusionsBSHXF could inhibit cartilage degradation through TGF-β/MMP13 signaling, and be considered a good option for the treatment of OA.
Highlights
Articular cartilage degeneration plays a key role in the pathogenesis of osteoarthritis (OA)
Bushen‐ huoxue formula (BSHXF) decelerates destabilization of the medial meniscus (DMM)‐induced OA progression Alcian Blue Hematoxylin/Orange G and Toluidine Blue staining revealed that prominent focal cartilage defects, early osteophyte formation and increases in subchondral bone mass was observed in DMM-induced mice compared to sham group
We evaluated the cartilage degradation through Osteoarthritis Research Society International (OARSI) grading, and we found that mice in BSHXF group had significantly lower scores compared to model mice (P < 0.01), with significantly reduced OARSI
Summary
Articular cartilage degeneration plays a key role in the pathogenesis of osteoarthritis (OA). Bushen‐ huoxue formula (BSHXF) has been widely used in the treatment of OA in clinics. The molecular mechanisms responsible for the chondroprotective effect of BSHXF remain to be elucidated. The purpose of this study was to explore the effects of BSHXF on OA mice model. Osteoarthritis (OA) which is characterized by abnormal extracellular matrix content (EMC) as well as articular surface erosion, is the most common disabling disease of the joint tissue influenced by interactions among age, genetic and mechanical factors [1]. There are a variety of treatment options for OA, but much emphasis in its early stage has been placed on pain relief through medication. The long-term uses of these drugs may induce prominent side effects. Current OA therapies could not ameliorate all the symptoms and are not considered to be disease modifying approaches [4]
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