Molecular mechanisms of polysaccharide components of kidney-tonifying traditional Chinese medicine in regulating osteoporosis

Osteoporosis, a prevalent systemic skeletal disorder, poses a significant health risk to the elderly population, arising from a multitude of factors that disrupt bone homeostasis. This delicate balance is primarily regulated by the dynamic interplay between osteoblasts and osteoclasts. When this equilibrium is perturbed, osteoporosis can ensue. Traditional Chinese Medicine (TCM) posits that the kidney, as the repository of vital essence, is instrumental in the production of bone marrow, which in turn confers skeletal strength. Consequently, TCM therapies that focus on kidney replenishment are frequently employed in the management of osteoporosis and other bone-related conditions. The polysaccharide metabolites of these TCM, which are designed to invigorate the kidney, exhibit a spectrum of pharmacological activities and engage multiple targets, such as Wnt and BMP-2/Smads signaling pathway activation and oxidative stress reduction. Notably, the protective and therapeutic roles of these polysaccharides in osteoporosis are mediated through distinct mechanisms and pathways. This review provides an overview of the application of the polysaccharide metabolites of kidney-tonifying TCM in the field of osteoporosis, with special emphasis on the mechanisms underlying the pharmacological effects of the various polysaccharide metabolites. It meticulously examines the precise molecular underpinnings and pathways through which these polysaccharides influence osteogenesis and osteoclastogenesis, with the aim of providing a robust foundation for future investigative endeavors and clinical applications of these polysaccharide metabolites in TCM kidney-tonifying therapies. This review summarizes preclinical evidence from animal and cell studies. However, clinical translation remains limited as most findings await validation in human trials. Moreover, this review aims to bolster the empirical evidence supporting the TCM principle that "the kidney governs the bones," thereby enriching the understanding and practical application of this ancient medical wisdom in contemporary healthcare settings.