Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases.

Rheumatoid arthritis (RA) and postmenopausal osteoporosis (PMOP) are common bone-immune diseases. The imbalance between helper (Th17) and regulatory T cells (Tregs) produced during differentiation of CD4+ T cells plays a key regulatory role in bone remodelling disorders in RA and PMOP. However, the specific regulatory mechanism of this imbalance in bone remodelling in RA and PMOP has not been clarified. Identifying the regulatory mechanism underlying the Th17/Treg imbalance in RA and PMOP during bone remodelling represents a key factor in the research and development of new drugs for bone immune diseases. In this review, the potential roles of Th17, Treg, and Th17/Treg imbalance in regulating bone remodelling in RA and PMOP have been summarised, and the potential mechanisms by which probiotics, traditional Chinese medicine compounds, and monomers maintain bone remodelling by regulating the Th17/Treg balance are expounded. The maintenance of Th17/Treg balance could be considered as an therapeutic alternative for the treatment of RA and PMOP. This study also summarizes the advantages and disadvantages of conventional treatments and the quality of life and rehabilitation of patients with RA and PMOP. The findings presented her will provide a better understanding of the close relationship between bone immunity and bone remodelling in chronic bone diseases and new ideas for future research, prevention, and treatment of bone immune diseases.

Research Progress on the Mechanism of the SFRP-Mediated Wnt Signalling Pathway Involved in Bone Metabolism in Osteoporosis.

Osteoporosis (OP) is a metabolic bone disease linked to an elevated fracture risk, primarily stemming from disruptions in bone metabolism. Present clinical treatments for OP merely alleviate symptoms. Hence, there exists a pressing need to identify novel targets for the clinical treatment of OP. Research indicates that the Wnt signalling pathway is modulated by serum-secreted frizzled-related protein 5 (SFRP5), potentially serving as a pivotal regulator in bone metabolism disorders. Moreover, studies confirm elevated SFRP5 expression in OP, with SFRP5 overexpression leading to the downregulation of Wnt and ß-catenin proteins in the Wnt signalling pathway, as well as the expression of osteogenesis-related marker molecules such as RUNX2, ALP, and OPN. Conversely, the opposite has been reported when SFRP5 is knocked out, suggesting that SFRP5 may be a key factor involved in the regulation of bone metabolism via the Wnt signalling axis. However, the molecular mechanisms underlying the action of SFRP5-induced OP have yet to be comprehensively elucidated. This review focusses on the molecular structure and function of SFRP5 and the potential molecular mechanisms of the SFRP5-mediated Wnt signalling pathway involved in bone metabolism in OP, providing reasonable evidence for the targeted therapy of SFRP5 for the prevention and treatment of OP.

Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.

Metabolic reprogramming is an adaptive response of tumour cells under hypoxia and low nutrition conditions. There is increasing evidence that glucose metabolism reprogramming can regulate the growth and metastasis of osteosarcoma (OS). Reprogramming in the progress of OS can bring opportunities for early diagnosis and treatment of OS. Previous research mainly focused on the glycolytic pathway of glucose metabolism, often neglecting the tricarboxylic acid cycle and pentose phosphate pathway. However, the tricarboxylic acid cycle and pentose phosphate pathway of glucose metabolism are also involved in the progression of OS and are closely related to this disease. The research on glucose metabolism in OS has not yet been summarized. In this review, we discuss the abnormal expression of key molecules related to glucose metabolism in OS and summarize the glucose metabolism related signaling pathways involved in the occurrence and development of OS. In addition, we discuss some of the targeted drugs that regulate glucose metabolism pathways, which can lead to effective strategies for targeted treatment of OS.

New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a form of iron-driven cell death. Mitophagy is a type of selective autophagy, where degradation of damaged mitochondria is the key mechanism for maintaining mitochondrial homeostasis. Additionally, Chaperone-mediated autophagy (CMA) is a biological process that transports individual cytoplasmic proteins to lysosomes for degradation through companion molecules such as heat shock proteins. Research has demonstrated the involvement of ferroptosis, mitophagy, and CMA in the pathological progression of Osteoarthritis (OA). Furthermore, research has indicated a significant correlation between alterations in the expression of reactive oxygen species (ROS), adenosine monophosphate (AMP)-activated protein kinase (AMPK), and hypoxia-inducible factors (HIFs) and the occurrence of OA, particularly in relation to ferroptosis and mitophagy. In light of these findings, our study aims to assess the regulatory functions of ferroptosis and mitophagy/CMA in the pathogenesis of OA. Additionally, we propose a mechanism of crosstalk between ferroptosis and mitophagy, while also examining potential pharmacological interventions for targeted therapy in OA. Ultimately, our research endeavors to offer novel insights and directions for the prevention and treatment of OA.