Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Zhang, Hao; Wang, Lipeng; Cui, Jin; Sicheng, Wang; Han, Yafei; Shao, Hongda; Wang, Cheng; Yan, Hu; Li, Xiaoqun; Zhou, Qirong; Guo, Jiawei; Xinchen, Zhuang; Sheng, Shihao; Zhang, Tao; Zhou, Dongyang; Chen, Jiao; Wang, Fuxiao; Gao, Qianmin; Jing, Yingying; Chen, Xiao; Su, Jiacan

doi:10.1126/sciadv.abo7868

Cited by 64 publications

(33 citation statements)

References 59 publications

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“…OA involves changes in the oxygen environment. Previous studies have revealed that hypoxic levels in the cartilage decreased as OA progressed, which is consistent with our finding of severe cartilage degeneration in the HH‐OA group 19,32 . Notably, chondrocyte clusters, which represent the proliferation and repair stage of OA cartilage, had relatively high hypoxic probe and HIF‐1α expression 33 .…”

Section: Discussionsupporting

confidence: 91%

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone

Li,

Yang,

Zhu

et al. 2024

The FASEB Journal

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A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high‐altitude environment. Micro‐computed tomography (Micro‐CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co‐culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH‐OA group compared to that in the normoxia‐OA (N‐OA) group, 4 weeks after surgery. Micro‐CT analysis revealed more deteriorated bone mass in the HH‐OA group than in the N‐OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH‐OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co‐culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH‐OA group. HH‐related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

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Section: Discussionsupporting

confidence: 91%

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone

Li,

Yang,

Zhu

et al. 2024

The FASEB Journal

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“…Osteoarthritis (OA) is a widespread irreversible articular disease marked by articular cartilage deterioration and subsequent osteophytes 1,2 . It affects millions of people worldwide, especially older people over 60 years old 3 .…”

Section: Introductionmentioning

confidence: 99%

Endothelial Stat3 activation promotes osteoarthritis development

Zhang

Liu

et al. 2023

Cell Proliferation

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The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H‐type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis‐mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H‐type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.

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“…In the pathogenesis of OA, abnormal osteophytes and bone remodeling of the subchondral bone were essential in determining the severity of the joint injury. [63][64][65] Severe ossification of the subchondral bone in OA rats resulted in the loss of normal mechanical structures (Fig. 7A).…”

Section: Hlc Improved Subchondral Bone Remodeling and Attenuated Cart...mentioning

confidence: 99%

Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation

An,

Zhou,

et al. 2024

J. Mater. Chem. B

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Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Cited by 64 publications

References 59 publications

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone

Endothelial Stat3 activation promotes osteoarthritis development

Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation

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