Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the “kidney governing bone” theory

Abstract

Background: Guzhi Zengsheng Zhitongwan (GZZSZTW) is an effective Chinese medicinal formulation for the treatment of osteoarthritis (OA) designed according to the "kidney governing bone" theory, which has been widely used as a golden guide for treating bone and cartilage diseases in traditional Chinese medicine. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney. Methods: Preparation and quality control were performed as previously described. Since GZZSZTW is orally administered in the form of pills prepared in boiled water, the Chinese materia medica (CMM) mixture of this formula was extracted with distilled water by a reflux method and was then filtered through a 0.45-μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80°C. The effects of GZZSZTW on gene expression and regulation of both kidney and bone tissues were investigated using a state-of-the-art RNA-seq technology. Results: We demonstrated that GZZSZTW could enhance kidney function and suppress bone formation and resorption by modulating the activities of osteoblast and osteoclast, and might subsequently contribute to the inhibition of osteophyte formation during the process of OA. These effects might be achieved by the synergistic interactions of various herbs and their active components in GZZSZTW, which increased the expression levels of functional genes participating in kidney function, regulation, and repair, and then decreased the expression levels of genes involved in bone formation and resorption. Thus, our findings were consistent with the "kidney governing bone" theory, which has been widely used as a guide in clinical practice for thousands of years. Conclusions: This study has deepened the current knowledge about the molecular effects of GZZSZTW on bone and kidney regulation. Furthermore, this study might be able to provide possible strategies to further prevent and treat joint diseases by using traditional Chinese medicinal formulations following the "kidney governing bone" theory.

Integrated RNA-Seq Analysis Uncovers the Potential Mechanism of the “Kidney Governing Bones” Theory of TCM

“…Previously, our group explored the molecular mechanisms related to bone development, growth, and regeneration using modern biology technologies, such as RNA-Seq and ITRAQ, and demonstrated that the underlying molecular mechanisms were highly consistent with the “kidney governing bones” theory. The results of this study coincide with our previous studies [ 6 – 10 ]. We also looked at markers for renal and testis function.…”

“…This means that the kidneys are responsible for the skeleton's growth and repair [ 5 ]. Previously, our group [ 6 – 10 ] explored the molecular mechanisms related to bone development, growth, and regeneration using modern biology technologies, such as RNA sequencing (RNA-Seq), and demonstrated that the underlying molecular mechanisms were highly consistent with the “kidney governing bones” theory. However, the precise molecular mechanism underlying “kidney governing bones” is still not clearly understood.…”

The enzymatic hydrolysates from deer sinew promote MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes

“…The enrichment analysis of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by R function phyper to determine the biological functions and signaling pathways of those identified DEGs. The significance of enriched functional clusters and signaling pathways were determined based on the adjusted p value (Q value) of less than 0.05, which was calculated according to the Hypergeometric test and Bonferroni correction [ 22 ].…”

Gujin Dan is a Chinese medicine formulation that stimulates cell proliferation and differentiation by controlling multiple genes involved in MC3T3-E1 cells

“…It has been shown that MC3T3-E1 is a continuous source of osteoblast regeneration that avoids the need for repeated preparation of primary osteoblasts and has a better balance and homogeneity than primary osteoblasts [8,9]. Gujin Dan (GJD), developed by Professor Liu Bailing, is one of the typical Chinese medicine, which consists of 19 herbs acting synergistically, and has been used for decades in the treatment of cervical spondylosis, lumbar disc herniation, osteoarthritis and osteoporosis in the Department of Orthopaedics and Traumatology of Jilin Province Hospital of Traditional Chinese Medicin, China [10][11][12]. Clinically, the formulation is usually in the form of an oral pill for the treatment of patients with osteoporosis.…”