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Updated: Sep 15, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Vitamin D Alleviates Osteoarthritis Progression by Targeting Cartilage and Subchondral Bone via Myd88-TAK1-ERK Axis
Xiang Gao1,2, Yalin Min1,3, Rui Lin1
1Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang City, Guangdong Province, 524045, People's Republic of China.
Background:
Osteoarthritis (OA) causes irreversible joint damage, but current treatments fail to fully address its complex pathology. Emerging evidence suggests subchondral bone metabolic dysfunction may initiate OA. While vitamin D (VitD) is well-established for bone metabolism regulation in osteoporosis, its therapeutic potential in OA remains unclear despite observational studies suggesting protective effects. Our integrated in vivo/in vitro study demonstrates VitD's dual chondroprotective and osteogenic actions in OA.
Methods:
Sprague-Dawley rats (n=24) were divided into three groups: sham operation (Sham), OA model (OA), and OA+VitD treatment, with 8 rats in each group. Oral cholecalciferol (2.34 μg/kg/day) was administered for 6 weeks post-Monosodium iodoacetate (MIA) induction. The therapeutic potential of vitamin D was evaluated through a series of in vivo experiments. Human chondrocyte C28 cells were pretreated with TNFα (1ng/mL) to model inflammatory injury, followed by 1,25(OH)2 D3 (10-2 μM) exposure for 72 hours to assess the VitD's effects of chondrogenesis and further investigate its underlying mechanism.
Results:
In OA rats, VitD suppressed femoral cartilage degradation (evidenced by 567.76% increased cartilage area, and 39.13% decreased Osteoarthritis Cartilage Histopathology (OACH) score and enhanced subchondral bone mass (61.81% higher BV/TV). At the molecular level, VitD downregulated the expression of cartilage matrix metalloproteinase 13 (MMP13), with a reduction of 74.72% compared to OA group. Additionally, VitD inhibit inflammatory signaling pathways, particularly through the MyD88-TAK1-ERK axis in chondrocytes, and decrease serum IL-6 level. Mechanistic validation of these findings was demonstrated by protein expression reduction of Myd88 (31.22%), phospho-ERK1/2 (66.11%), AP-1 (61.43%) and NFκB (34.36%) compared to OA group. In vitro, VitD also rescued ethanol-induced C28 cell viability loss while significantly upregulating cartilage anabolic markers.
Conclusion:
These findings establish VitD as a multimodal OA therapeutic agent targeting both cartilage catabolism and subchondral bone remodeling through Myd88-TAK1-ERK axis.
Insights
Vitamin D (VitD) shows promise for osteoarthritis (OA) treatment by protecting cartilage and improving bone health. This study reveals VitD
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is characterized by irreversible joint damage, with current treatments being insufficient.
- Subchondral bone metabolic dysfunction is increasingly recognized as an initiator of OA.
- The role of vitamin D (VitD) in OA pathogenesis and treatment is not fully understood, despite its known role in bone metabolism.
Purpose of the Study:
- To investigate the therapeutic potential of vitamin D (VitD) in osteoarthritis (OA).
- To evaluate the dual chondroprotective and osteogenic effects of VitD in an OA model.
- To elucidate the molecular mechanisms underlying VitD's action in OA.
Main Methods:
- An in vivo study using Sprague-Dawley rats with surgically induced OA, treated with oral cholecalciferol.
- An in vitro study using human chondrocyte C28 cells exposed to TNFα and 1,25(OH)2D3.
- Assessment of cartilage degradation, subchondral bone mass, gene expression (MMP13), and inflammatory signaling pathways (MyD88-TAK1-ERK axis).
Main Results:
- VitD treatment significantly suppressed femoral cartilage degradation and enhanced subchondral bone mass in OA rats.
- VitD downregulated MMP13 expression and inhibited inflammatory signaling pathways, including the MyD88-TAK1-ERK axis in chondrocytes.
- In vitro, VitD rescued chondrocyte viability and upregulated anabolic markers.
Conclusions:
- Vitamin D demonstrates multimodal therapeutic potential for OA, targeting both cartilage catabolism and subchondral bone remodeling.
- The MyD88-TAK1-ERK pathway is identified as a key mechanism through which VitD exerts its effects in OA.
- VitD represents a promising therapeutic agent for osteoarthritis management.
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