Breast Cancer Risk Factors Analysis in Middle-Aged Women: Evidence From a Cross-Sectional Epidemiological Study.

Articular cartilage, lining the ends of opposing bones within synovial joints, is a connective tissue characterized by thinness, smoothness, and viscoelastic properties. This tissue features a high extracellular matrix content (up to 95% by volume) and a sparse chondrocyte population (). It is essential for load distribution, shock absorption, friction minimization, and joint stability (, ). However, its intrinsic regenerative capacity is still a clinical challenge due to the absence of microvessels, lymphatic vessels, and neural networks, and this deficiency often leads to the expansion of articular cartilage damage into surrounding tissues such as the peripheral synovium and subchondral bone, ultimately initiating an irreversible cascade of symptoms including joint pain, stiffness, and functional impairment (). Cartilage injury and subsequent irreversible degeneration are the main hallmark events of osteoarthritis, which is considered to be a type of lipid metabolism disorder with symptoms similar to systemic metabolic syndrome (). Interestingly, a notable structural and metabolic feature of articular cartilage is its capacity to act as a lipid reservoir. Cartilage internalizes lipids diffusing from adjacent tissues and stores them either within the extracellular matrix or as cytoplasmic lipid droplets in chondrocytes, providing a readily available energy substrate for cellular metabolism (, ). Lipid droplets are assembled around a core of neutral lipids, predominantly triacylglycerols and cholesterol esters, and are bounded by a phospholipid monolayer that is studded with specific surface proteins (). They are first synthesized in the endoplasmic reticulum through the aggregation and budding of neutral lipids (). During their maturation, tiny lipid droplets uptake lipids from the surface of endoplasmic reticulum, coalesce with smaller lipid particles, and fuse into larger ones (). Serving as dynamic storage and transport systems for lipids, lipid droplets tightly participate in lipid metabolism, including lipolysis, lipophagy and lipogenesis, in response to cellular metabolic and energetic demands (). Through the dynamic inter-organellar contact with the endoplasmic reticulum, mitochondria, Golgi apparatus, peroxisomes, and lysosomes, lipid droplets also serve as central hubs for organelle assembly, membrane synthesis/trafficking, ion signaling, protein degradation, and autophagy (). Additionally, lipid droplets are involved in defense against lipotoxicity, regulation of oxidative stress, intervention in inflammatory and immune responses, and even shaping of the genomic landscape (). In cartilage, previous evidence has revealed that excessive lipid droplet accumulation in chondrocytes can contribute to structural and functional damage to cartilage layers and trigger osteochondral diseases such as osteoarthritis (, ). Research from Park . showed that acetyl-CoA thioesterase 12 (Acot12) knockout-driven lipid droplet accumulation increased metabolic stress, impaired chondrocyte cellularity, and exacerbated cartilage degradation in osteoarthritis (). In contrast, Lee . reported that lipid droplet accumulation mediated by protein kinase casein kinase 2 (Pkck2), six-transmembrane protein of prostate 2 (Stamp2), and fat-specific protein 27 (Fsp27) protected chondrocytes from lipotoxicity and represented a potential target for osteoarthritis interventions (). However, the mechanism of chondrocyte lipid droplet formation and its importance in disease occurrence is still insufficiently understood. Lipid droplet-associated protein regulators orchestrate the dynamic life cycle of lipid droplets through controlling lipid droplet formation, enlargement, merging, breakdown, and inter-organellar communication (). These proteins can be categorized into multiple functional groups, including enzymes involved in lipid metabolism, membrane transporters facilitating organelle interactions, histones linking lipid droplets to nucleic acids, ribosomal proteins engaged in prokaryotic protein synthesis, protein degradation-associated proteins, and other signaling molecules (). In this context, the fatty acid-binding protein (Fabp) family is considered to play an important role in the formation and function of lipid droplets. Fabps are highly conserved and widely expressed lipid chaperones with molecular weights ranging from 14 to 15 kDa (). Characterized by a distinctive hydrophobic pocket, Fabps enable the reversible binding of fatty acids (), which allows them to facilitate lipid metabolic compartmentalization by directing lipids to specific organelles, thereby regulating storage in lipid droplets, membrane biogenesis in the endoplasmic reticulum, oxidative breakdown in mitochondria and peroxisomes, and transcriptional control within the nucleus ().