Bone marrow lesions (BML) are early signs of osteoarthritis (OA) and are strongly correlated with the deterioration of cartilage lesions. Single-cell RNA sequencing (scRNA-seq) analyses were performed on BM from non-BML and BML areas and articular cartilage from intact and damaged areas to explore BML landscape and BML-cartilage crosstalk. We revealed the immune landscape of BM in non-BML and BML, and the transition to pro-inflammatory states of clusters in BMLs, such as classical monocytes and non-classical monocytes. Non-classical monocytes have high inflammation, OA gene signatures, and senescence scores, and are potential primary clusters promoting OA progression. Histological signs of OA related to the cellular landscape in damaged cartilage were identified, including PreFC exhaustion. The BM-cartilage crosstalk at the cell-cell interaction (CCIs) level and the TNF signal transmitted by non-classical monocytes are the critical CCIs in BML-induced cartilage damage, and PreFC is one of the primary receivers of the signal. We further validated the higher senescence level of non-classical monocyte and FC-2 in OA mice, compared with classical monocyte and PreFC, respectively. Transcription factor 7 like 2 (TCF7L2) was identified as a shared transcription factor in the senescence of monocytes and chondrocytes, facilitating the development of the senescence-associated secretory phenotype (SASP). Therefore, senescent non-classical monocytes promote BMLs and inflammation and senescence of chondrocytes by modulating BML–cartilage crosstalk in OA, with TCF7L2 serving as a regulator.

Cuproptosis, a newly identified form of cell death, presents an as-yet-unclear potential correlation with Osteoarthritis (OA) pathogenesis. This study aimed to explore the relationship between chondrocyte cuproptosis and OA, and to evaluate the therapeutic potential of the copper ion chelator tetrathiomolybdate (TTM) in OA treatment. We collected clinical cartilage samples and animal specimens, employing Micro-CT, histopathological staining, immunohistochemistry, and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to evaluate the potential occurrence of chondrocyte cuproptosis during OA progression. In vitro, we used elesclomol and copper sulfate to create a cuproptosis model in mouse chondrocytes. Techniques like ICP-MS, CCK-8, and others were used to explore the role of cuproptosis in OA development. To assess if TTM can mitigate chondrocyte cuproptosis and decelerate OA progression, various methods were applied at cellular and animal levels. Metabolomics predicted pathways for TTM's potential OA improvement. Molecular docking was employed to predict the intervention target of TTM. The impact of glutathione (GSH) on chondrocyte cuproptosis and OA development was studied using si-glutathione synthetase (si-GSS) plasmid knockdown and exogenous GSH supplements. Our findings indicate that in the process of OA, chondrocytes show an increase in copper ion content, metabolic disorders of the cartilage matrix, low expression of cuproptosis - related proteins lipoamide dehydrogenase (DLAT), dihydrolipoamide succinyltransferase (DLST), and ferredoxin 1 (FDX1), and high expression of the heat shock protein70 (HSP70). As the primary target of cuproptosis, mitochondria experience significant impacts on respiratory function and morphology during this process. TTM enhances chondrocytes resistance to cuproptosis by promoting GSH expression, thus ameliorating the OA phenotype. Chondrocyte cuproptosis is integral to pathogenesis and progression of OA, and TTM has emerged as a novel and potentially valuable therapeutic strategy for the treatment of this disease. Chondrocyte cuproptosis plays a key role in the occurrence and development of knee osteoarthritis. The copper ion chelator (Tetrathiomolybdate) has been proved to be able to treat knee osteoarthritis by alleviating chondrocyte cuproptosis.

Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti‐infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti‐infective treatment. Epimedium‐Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro‐CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP‐CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA‐34a‐5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF‐β signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP‐CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR‐34a‐5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF‐β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS‐induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA‐34a‐5p/ SMAD2 in IBDs.