关键词: 激素性股骨头坏死, 关节软骨, 软骨下骨, 软骨细胞, 新月征

Abstract: BACKGROUND: The crescent sign is a significant radiological feature in the progression of steroid-induced osteonecrosis of the femoral head (SIONFH), indicating the separation and defect of articular cartilage and subchondral bone. The appearance of the crescent sign is associated with the mid-to-late stages of the disease and poor prognosis. However, studies on the specific pathological characteristics and progression patterns of articular cartilage in SIONFH are limited.
OBJECTIVE: To observe the pathological features of articular cartilage in SIONFH specimens at different stages, explore the underlying pathological mechanisms, and elucidate the formation mechanism of the crescent sign, providing a theoretical basis for optimizing hip-preserving strategies.
METHODS: Femoral head specimens from SIONFH patients who underwent total hip replacement surgery at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2021 to 2024 were selected. According to the ARCO staging system, the specimens were divided into mild, moderate, and severe collapse groups, with fresh femoral neck fracture specimens as the control group. All specimens were coronally sectioned, and the necrotic cartilage surface was obtained for histological staining (hematoxylin-eosin, Safranin O-fast green) and pathological assessment. Immunohistochemical staining was used to detect bone and cartilage-related protein expression, while Western blotting was employed to measure the expression levels of relevant proteins. An apoptosis kit was used to detect the level of apoptosis in articular cartilage.
RESULTS AND CONCLUSION: (1) Gross observation revealed that the control group had smooth cartilage surfaces without wrinkling or proliferation, and no separation defects between articular cartilage and subchondral bone, which was strong but pliable in texture. In contrast, SIONFH specimens exhibited significant wrinkling of the cartilage surface, with separation defects between articular cartilage and subchondral bone, which felt relaxed upon palpation. (2) Pathological observation of the femoral head showed that in the control group, chondrocytes were orderly arranged, the cartilage matrix was uniformly stained, the tidemark was intact and continuous, and the calcified cartilage layer was clearly connected to the subchondral bone with orderly trabecular arrangement. In SIONFH specimens, chondrocytes were disordered, with increased empty lacunae, varying degrees of matrix staining loss, duplication and loss of the tidemark, numerous cavities and sclerosis in the calcified cartilage layer, and invasion of granulation tissue into these cavities. Separation defects were observed between calcified cartilage and subchondral bone, with abundant granulation tissue in the subchondral bone trabecular spaces. (3) Immunohistochemical analysis revealed increased positive staining for Runt-related transcription factor 2, matrix metalloproteinase 13, matrix metalloproteinase 3, type I collagen alpha 2 chain in the calcified cartilage layer and deep cartilage of SIONFH specimens. Increased positive staining for vascular endothelial growth factor A, hypoxia-inducible factor 1α, interleukin 1β, tumor necrosis factor α was observed in the subchondral bone trabecular spaces and granulation and scar tissues of deep cartilage. (4) Western blot results showed decreased expression of type II collagen α1 chain and SOX9 proteins, and increased expression of Runt-related transcription factor 2, matrix metalloproteinase 13, hypoxia-inducible factor 1α, and vascular endothelial growth factor A in SIONFH specimens. (5) Caspase 3/7 activity was significantly higher in SIONFH specimens than the control group and was positively correlated with the degree of collapse. In conclusion, articular cartilage lesions in SIONFH patients are primarily concentrated in the deep and calcified cartilage areas surrounding the necrotic zone. Subchondral bone tissue necrosis leads to changes in the local microenvironment and elastic modulus, causing sclerosis of the calcified cartilage. As the femoral head continues to bear weight, stress concentration in the sclerotic area around the necrotic zone leads to brittle fractures, initiating the crescent sign. Fracture of bone and cartilage disrupts the subchondral cortical bone barrier, and invasion of granulation tissues into the subchondral bone trabecular spaces directly stimulates calcified and deep cartilage, resulting in terminal differentiation and apoptosis of chondrocytes, matrix degradation, and cavity formation. This leads to a decline in the repair capacity of articular cartilage. The affected cartilage cannot properly integrate with the subchondral bone, further exacerbating joint cartilage wear. As the disease progresses, extensive separation defects between bone and cartilage occur, manifesting as the crescent sign on imaging.

Key words: steroid-induced osteonecrosis of the femoral head, articular cartilage, subchondral bone, chondrocyte, crescent sign