Osteochondral junction is a functional unit comprising the articular cartilage, calcified cartilage, and subchondral bone. Alteration in any component of this composite unit can disrupt the joint integrity and function directly or indirectly. Biochemical signals mediate the crosstalk between tissues and play an essential role in the initiation and progression of osteoarthritis. As osteoarthritis progresses, abnormal subchondral bone remodelling leads to increased angiogenesis and porosity of the subchondral bone plate, which further triggers biochemical signals to mediate the crosstalk between cartilage and bone, contributing to the progression of osteoarthritis. Notably, common biochemical signals include the TGF‐β/Smad, Wnt/β‐catenin, RANK/RANKL/OPG, and MAPK pathways. This biomarker crosstalk network is the basis of osteoarthritis pathogenesis, and some of their key regulators may be potential therapeutic targets for osteoarthritis drug therapy. This review summarised the biochemical crosstalk between cartilage and bone in the pathogenesis of osteoarthritis, which may provide the basis for the discovery of osteoarthritis treatment targets.

Estrogen levels are the core factor influencing postmenopausal osteoporosis (PMOP). Estrogen can affect the progression of PMOP by regulating bone metabolism, influencing major signaling pathways related to bone metabolism, and modulating immune responses. When estrogen levels decline, the activity of Sirtuins (SIRTs) is reduced. SIRTs are enzymes that function as NAD+-dependent deacetylases. SIRTs can modulate osteocyte function, sustain mitochondrial homeostasis, and modulate relevant signaling pathways, thereby improving bone metabolic imbalances, reducing bone resorption, and promoting bone formation. In PMOP, SIRT1, SIRT3, and SIRT6 are primarily affected. Oxidative stress (OS) is a crucial factor in PMOP, as it generates excessive reactive oxygen species (ROS) that exacerbate PMOP. There is a certain interplay between SIRTs and OS. The reduced activity of SIRTs leads to intensified OS and the excessive accumulation of ROS. In return, ROS suppresses the AMPK signaling pathway and the synthesis of NAD+, which consequently diminishes the function of SIRTs. Natural SIRT activators and natural antioxidants, which are characterized by high safety, convenience, and minimal side effects, represent a potential therapeutic strategy for PMOP. This study aims to investigate the mechanisms of SIRTs and OS in PMOP and summarize potential therapeutic strategies to assist in the improvement of PMOP.

Background: The purpose of this study was to explore whether moderate-intensity exercise can alleviate motion-induced post-traumatic osteoarthritis (PTOA) and the expression change of lncRNA H19 during this progression.Methods: Twenty-week-old male C57BL/6 mice were randomly divided into five groups: model control group (MC group,n = 6), treadmill model group (M group,n = 6), rehabilitation control group (RC group,n = 6), treadmill model + rehabilitation training group (M + R group,n = 6) and treadmill model + convalescent group (M + C group,n = 6). Paraffin sections were used to observe the pathological changes in the mouse knee joint in each group. A micro-CT was used to scan the knee joint to obtain the morphological indexes of the tibial plateau bone. Real-time PCR was used to detect the mRNA levels of inflammatory factors, synthetic and catabolic factors in cartilage.Results: After high-intensity exercise for 4 weeks, the inflammation and catabolism of the mouse knee cartilage were enhanced, and the anabolism was weakened. Further study showed that these results were partially reversed after 4-week moderate-intensity training. The results of hematoxylin–eosin staining confirmed this finding. Meanwhile, high-intensity exercise reduced the expression of lncRNA H19 in cartilage, while the expression of lncRNA H19 increased after 4 weeks of moderate-intensity exercise.Conclusion: High-intensity treadmill running can cause injury to the knee cartilage in C57BL/6 mice which leads to PTOA and a decrease of lncRNA H19 expression in cartilage. Moderate-intensity exercise can relieve PTOA and partially reverse lncRNA H19 expression.

Heart failure represents the terminal stage in the development of many cardiovascular diseases, and its pathological mechanisms are closely related to disturbances in energy metabolism and mitochondrial dysfunction in cardiomyocytes. In recent years, nicotinamide adenine dinucleotide (NAD⁺), a core coenzyme involved in cellular energy metabolism and redox homeostasis, has been shown to potentially ameliorate heart failure through the regulation of mitochondrial function. This review systematically investigates four core mechanisms of mitochondrial dysfunction in heart failure: imbalance of mitochondrial dynamics, excessive accumulation of reactive oxygen species (ROS) leading to oxidative stress injury, dysfunction of mitochondrial autophagy, and disturbance of Ca²⁺ homeostasis. These abnormalities collectively exacerbate the progression of heart failure by disrupting ATP production and inducing apoptosis and myocardial fibrosis. NAD⁺ has been shown to regulate mitochondrial biosynthesis and antioxidant defences through the activation of the deacetylase family (e.g., silent information regulator 2 homolog 1 (SIRT1) and SIRT3) and to increase mitochondrial autophagy to remove damaged mitochondria, thus restoring energy metabolism and redox balance in cardiomyocytes. In addition, the inhibition of NAD⁺-degrading enzymes (e.g., poly ADP-ribose polymerase (PARP), cluster of differentiation 38 (CD38), and selective androgen receptor modulators (SARMs)) increases the tissue intracellular NAD⁺ content, and supplementation with NAD⁺ precursors (e.g., β-nicotinamide mononucleotide (NMN), nicotinamide riboside, etc.) also significantly elevates myocardial NAD⁺ levels to ameliorate heart failure. This study provides a theoretical basis for understanding the central role of NAD⁺ in mitochondrial homeostasis and for the development of targeted therapies for heart failure.

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.

Perimenopausal women have fluctuating estrogen levels, which often trigger a range of symptoms of perimenopausal syndromes as estrogen levels decrease. Changes in perimenopausal estrogen levels are closely related to pain in knee osteoarthritis (KOA), which has long been a research area of great interest in perimenopausal women. In recent years, it has been found that perimenopausal estrogen levels have an important role in KOA pain, namely, that estrogen can affect KOA pain through the regulation of inflammatory responses, inhibition of cellular senescence and apoptosis, and modulation of neurotransmitters, which may provide new ideas for KOA treatment. This study aims to describe the mechanism of estrogen level on knee osteoarthritis pain in perimenopause and related non-pharmacological measures, such as physical therapy, physical factor therapy, traditional Chinese medicine, and diet, which can provide a reference for the study and treatment of pain in perimenopausal women with KOA.