Chongrenside D from Smilax china L protects against inflammation-induced joint destruction via inhibiting osteoclastogenesis
Yanxiang Liang,
Tian Qin,
Caixia Pang,
Xinru Yang,
Zongbin Wu,
Xiaolian Liao,
Jie Zhang,
Siyu Zeng,
Chun Zhou,
Cuiling Liu
Affiliations
Yanxiang Liang
Department of Pharmacy, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518101, China; School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China
Tian Qin
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China
Caixia Pang
Department of Pharmacy, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518101, China
Xinru Yang
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China
Zongbin Wu
Department of Pharmacy, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518101, China
Xiaolian Liao
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China
Jie Zhang
Department of Pharmacy, Guangdong Provincial Hospital of Chinese Medicine. the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, China
Siyu Zeng
Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China; Corresponding author. Deparment of Pharmacy, Guangdong Second Provincial General Hospital, No. 466 Xingang Middle Road, Haizhu District, Guangzhou, 510317, China.
Chun Zhou
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China; Corresponding author. SMU-KI United Medical Inflammatory Center, School of Pharmaceutical Sciences, Southern Medical University, No. 1023Shatai South Road, Baiyun District, Guangzhou, 510515, China.
Cuiling Liu
Department of Pharmacy, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518101, China; Corresponding author. Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518101, China.
Background: Bone-destructive diseases including rheumatoid arthritis (RA), osteoporosis, and bone metastases, are increasingly prevalent and worrisome due to the over-activated of osteoclasts. Chongrenside D (CGD) is a furostanol saponin extracted from Smilax china L, which has been demonstrated to have anti-inflammatory properties in our previous research. However, its effect on rheumatoid arthritis, especially on osteoclast differentiation and bone destruction has not yet been investigated. Methods: We evaluated the toxicity of CGD on the cell we used, RANKL-induced osteoclast formation, bone resorption activity, and osteoclast-specific genes or protein expression using bone marrow-derived monocytes (BMMs) -derived osteoclasts. Furthermore, the protective function of CGD on the paws of osteolytic mice was carried out using micro-CT, H&E, TRAP staining, as well as real-time PCR, and western blotting. Inflammatory cytokine levels were conducted through ELISA assay. The relative signaling pathways were investigated using western blotting, immunofluorescence microscopy and real-time PCR. Results: CGD notably inhibited RANKL-induced osteoclast formation, and suppressed the expression of osteoclast markers and actin ring formation, thus attenuating its bone resorption activity. For in vivo work, CGD protected against joint bone destruction induced by LPS, increased trabecular number and thickness, and reduced trabecular separation. CGD also inhibited the levels of inflammatory cytokines IL-6and TNF-α, improved the integrity of joint bones and decreased TRAP-positive staining area. The mechanistic study indicated that CGD down-regulated MMP9 and FAK-Src signaling, which were crucial for the resorption function of osteoclasts. CGD also inhibited MAPK pathway-mediated cell differentiation and survival, finally resulting in weak osteoclastogenesis. Conclusion: CGD exerts a significant anti-osteolytic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclastogenesis and function. Consequently, our study indicated that CGD may have a potential therapeutic role in the precaution of osteolytic bone disease.
