The Role of Hemoglobin in Temporomandibular Joint Osteoarthritis and the Therapeutic Potential of Hydroxyurea

  • Int J Dent. 2026 May 19:2026:3607127. doi: 10.1155/ijod/3607127.
Min Hui  1  2 ,  Zhihua Xu  2 ,  Qinghua Li  2 ,  Ying Zhan  2 ,  Yuqian Shi  2 ,  Fan Wu  2 ,  Lei Lu  2 ,  Mian Zhang  2 ,  Hongxu Yang  2 ,  Shibin Yu  2 ,  Jing Zhang  2
Affiliations
  • 1. School of Medicine, Northwest University, Xi'an, Shaanxi, China, nwu.edu.cn.
  • 2. State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China, fmmu.edu.cn.
PMID: 42164273 DOI: 10.1155/ijod/3607127
Abstract

Background: Temporomandibular joint osteoarthritis (TMJ OA) is characterized by articular cartilage degeneration involving chondrocyte loss and matrix degradation. However, the underlying mechanisms remain elusive. Hemoglobin (HB) has been identified in chondrocytes and is closely associated with cell survival.

Objective: This study aims to investigate the role of HB in condylar cartilage degeneration during the early stage of TMJ OA and evaluate the potential protective effects of hydroxyurea (HU), a therapeutic agent used for sickle cell disease, suggesting its promise as a novel therapeutic strategy against OA.

Methods: The TMJ OA model was established in 6-week-old female rats using unilateral anterior crossbite (UAC). ATDC5 chondrocytes were exposed to fluid flow shear stress (FFSS) to mimic OA-like changes in vitro. Histological and immunohistochemical staining, Real-Time PCR, and Western blot analysis were performed to detect the morphological and molecular changes in condylar cartilage.

Results: The results showed a significant downregulation of HBA and HBB alongside cartilage degeneration in the UAC group, characterized by decreased cartilage thickness, degraded cartilage matrix, and increased Matrix Metalloproteinases (MMPs). FFSS-stimulated chondrocytes also exhibited decreased HBA and HBB expression. Notably, HU treatment enhanced γ-globin gene (HBG) expression, mitigated FFSS-stimulated chondrocyte degeneration in vitro, and attenuated TMJ OA progression in vivo. Specifically, HU ameliorated the degenerative phenotype in cartilage, increasing matrix content and reducing matrix-degrading enzyme expression.

Conclusions: These findings identify HB subunits as novel molecular targets for OA therapy, with HU demonstrating significant chondroprotective efficacy. The study provides mechanistic insights into OA pathogenesis and highlights a promising repurposing therapeutic strategy for clinical intervention.

Keywords
cartilage; condyle; hemoglobin; hydroxyurea; osteoarthritis; temporomandibular joint.
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