Abstract
BackgroundRehmanniae Radix is a traditional herbal medicine in East Asia that has been widely used to treat patients with osteoporosis. However, the effect of catalpol, the primary active principle component of Rehmanniae Radix, on the function of bone marrow mesenchymal stem cells (BMSCs) and the underlying molecular mechanisms associated with its activity remain poorly understood.MethodsThe effect of catalpol on the proliferation of BMSCs was evaluated using a Cell Counting Kit-8 assay. Alkaline phosphatase (ALP) staining, ALP activity and Alizarin Red staining were performed to elucidate the effect of catalpol on the osteogenesis of BMSCs. qRT-PCR, Western blotting and immunofluorescence were performed to evaluate the expression of osteo-specific markers and the Wnt/β-catenin signalling-related genes and proteins. Moreover, a rat critical-sized calvarial defect model and a rat ovariectomy model were used to assess the effect of catalpol on bone regeneration in vivo.ResultsCatalpol significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity and calcium deposition in BMSCs in vitro. This phenomenon was accompanied by an upregulation of Wnt/β-catenin signalling. In addition, the enhanced osteogenesis due to catalpol treatment was partially reversed by a Wnt/β-catenin antagonist. Furthermore, catalpol increased the bone healing capacity of BMSCs in a rat critical-sized calvarial defect model and attenuated bone loss in a rat ovariectomy model.ConclusionsThese data suggest that catalpol enhances the osteogenic differentiation of BMSCs, partly via activation of the Wnt/β-catenin pathway. Catalpol may provide a new strategy for bone tissue engineering and can be a potential agent for the treatment of postmenopausal osteoporosis.
Highlights
Rehmanniae Radix is a traditional herbal medicine in East Asia that has been widely used to treat patients with osteoporosis
Alkaline phosphatase (ALP) is an early marker of osteogenesis, and enhanced ALP staining and higher ALP activity were observed in the catalpol treatment groups compared to the control group (P < 0.05), while no significant differences were observed between the 10, 50 and 250 μM catalpol treatment groups (P > 0.05) (Fig. 1c, d)
The number of calcium deposits, which was examined by Alizarin Red staining, was significantly increased after catalpol treatment (P < 0.05), and the mineralization was significantly enhanced in the 50 and 250 μM groups compared with that observed in the 10 μM group (P < 0.05)
Summary
Rehmanniae Radix is a traditional herbal medicine in East Asia that has been widely used to treat patients with osteoporosis. Osteoporosis is most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation [3]. The current clinical treatment for osteoporosis falls into two categories: antiresorptive agents that inhibit osteoclast function and anabolic agents that induce osteoblastic bone formation [4]. Zhu et al Stem Cell Research & Therapy (2019) 10:37 structure but cannot restore bone mass or architecture [1], and antiresorptive drugs such as bisphosphonates may lead to suppressed bone turnover after a long-term use [5, 6]. There is an urgent need to find a new and effective anabolic agent to treat osteoporosis
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