The intervertebral disc (IVD) is the largest avascular organ of the human body and plays a fundamental role in providing the spine with its unique structural and biomechanical functions. The inner part of the IVD contains the nucleus pulposus (NP), a gel-like tissue characterized by a high content of type II collagen and proteoglycans, which is crucial for the disc’s load-bearing and shock-absorbing properties. With aging and IVD degeneration (IDD), the NP gradually loses its physiological characteristics, leading to low back pain and additional sequelae. In contrast to surrounding spinal tissues, the NP presents a distinctive embryonic development since it directly derives from the notochord. This review aims to explore the embryology of the NP, emphasizing the pivotal roles of key transcription factors, which guide the differentiation and maintenance of the NP cellular components from the notochord and surrounding sclerotome. Through an understanding of NP development, we sought to investigate the implications of the critical developmental aspects in IVD-related pathologies, such as IDD and the rare malignant chordomas. Moreover, this review discusses the therapeutic strategies targeting these pathways, including the novel regenerative approaches leveraging insights from NP development and embryology to potentially guide future treatments.

Background Chronic low-back pain (LBP) is the largest contributor to disability worldwide, yet many assessments still reduce a complex, spatially distributed condition to a single 0–10 score. Body-map drawings capture location and extent of pain, but manual digitization is too slow and inconsistent for large studies or real-time telehealth. Methods Paper pain drawings from 332 adults in the multicenter COMEBACK study (four University of California sites, March 2021–June 2023) were scanned to PDFs. A Python pipeline automatically (i) rasterized PDF pages with pdf2image v1.17.0; (ii) resized each scan and delineated anterior/posterior regions of interest; (iii) registered patient silhouettes to a canonical high-resolution template using ORB key-points, Brute-Force Hamming matching, RANSAC inlier selection, and 3 × 3 projective homography implemented in OpenCV; (iv) removed template outlines via adaptive Gaussian thresholding, Canny edge detection, and 3 × 3 dilation, leaving only patient-drawn strokes; (v) produced binary masks for pain, numbness, and pins-and-needles, then stacked these across subjects to create pixel-frequency matrices; and (vi) normalized matrices with min–max scaling and rendered heat maps. RGB composites assigned distinct channels to each sensation, enabling intuitive visualization of overlapping symptom distributions and for future data analyses. Results Cohort-level maps replicated classic low-back pain hotspots over lumbar paraspinals, gluteal fold, and posterior thighs, while exposing less-recognized clusters along the lateral hip and lower abdomen. Neuropathic-leaning drawings displayed broader leg involvement than purely nociceptive patterns. Conclusions Our automated workflow converts pen-on-paper pain drawings into machine-readable digitized images and heat maps at the population scale, laying practical groundwork for spatially informed, precision management of chronic LBP.

Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive joint degeneration driven by extracellular matrix (ECM) breakdown, chondrocyte apoptosis, and chronic low-grade inflammation. Despite the availability of several pharmacological and non-pharmacological interventions, no current therapy effectively halts or reverses disease progression. Physical activity is traditionally recognized as a cornerstone in OA management, improving pain and functional outcomes; however, the molecular mechanisms underlying its beneficial effects remain partially understood. Irisin, a myokine generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 in response to muscle contraction, has recently emerged as a potential regulator of cartilage homeostasis. Experimental evidence indicates that irisin exerts pleiotropic effects by modulating inflammatory and catabolic signaling pathways, promoting anabolic and reparative processes, restoring autophagic and mitophagic flux, and preserving mitochondrial function. These actions collectively contribute to the maintenance of ECM integrity and chondrocyte viability. In vitro and in vivo studies consistently support the protective role of irisin in cartilage biology, highlighting its involvement in the muscle–cartilage axis and its potential as both a biomarker and therapeutic target for OA. This narrative review critically evaluates the chondrocyte-specific mechanisms, receptor uncertainties, experimental-model limitations, analytical challenges, and delivery strategies that currently define the biological and translational relevance of irisin in OA. Particular attention is given to the identification of irisin-mediated signaling pathways in chondrocytes, optimization of delivery strategies, and the definition of exercise regimens capable of maximizing its chondroprotective effects.