Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c-fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion

Fang, Chao; Guo, Jiawei; Wang, Yajun; Li, Xiaoqun; Zhang, Hao; Cui, Jin; Yan, Hu; Jing, Yingying; Chen, Xiao; Su, Jiacan

doi:10.1038/s41401-021-00747-9

Cited by 45 publications

(39 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies showed that targeting osteoclast abnormal activation could block abnormal subchondral bone remodeling in the very beginning and protect articular cartilage degeneration ( 27-30 ). Previously we reported that LPL, an actin-bundling protein, is indispensable for osteoclast fusion and resorption ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…Tibia subchondral bone vasculature was evaluated by Micro-CT as reported earlier ( 30 ). Mice were anesthetized with pentobarbital sodium, tibia subchondral bone vessels were washed with normal saline solution, 4% PFA solution and normal saline solution through heart in proper sequence.…”

Section: Methodsmentioning

confidence: 99%

“…Knee joints were collected and fixed in 4% PFA for 2 d, and decalcified in 10% EDTA for 14 d. Next, the joints were embedded in paraffin or OCT and serially sectioned 5-μm in the sagittal plane of in central the medial compartment of the joints. Then, hematoxylin and eosin (H&E, G1005-500ML, Servicebio, Wuhan, China), Safranin O and fast green (G1053-100ML Servicebio, Wuhan, China), and TRAP staining (G1050-50T, Servicebio, Wuhan, China) were done according to regular procedures (18,30) . A light microscope (Olympus BX53) was used for imaging.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Zhang

Wang

Cui

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Abnormal subchondral bone remodeling featured by over-activated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is still unclear. In this study, we used lymphocyte cytosolic protein 1 (Lcp1) knock-out mice to suppress subchondral osteoclast formation in mice OA model with anterior cruciate ligament transection (ACLT) and Lcp1-/- mice showed decreased bone remodeling and sensory innervation in subchondral bone accompanied by retarded cartilage degeneration. For mechanisms, in wildtype mice with ACLT the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration which ubiquitylated hypoxia-inducible factor 1α (HIF-1α), vital for maintaining chondrocyte homeostasis in articular chondrocytes and led to cartilage degeneration. Deletion of Lcp1 impeded osteoclast-mediated angiogenesis, which maintained the low levels of oxygen partial pressure (pO2) in subchondral bone as well as the whole joint and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Notably, we identified a novel subgroup of hypertrophic chondrocytes highly associated with OA by single cell sequencing analysis of human articular chondrocytes. Lastly, we showed that Oroxylin A, an Lcp1-encoded protein L-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment in subchondral bone is an attractive strategy for OA treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Zhang

Wang

Cui

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Taken together, we chose the OA mouse model established by ACLT, and there is no sexually dimorphic effect anticipated. Meanwhile, several research also included only female mice in OA studies 11,48 . Finally, C57Bl/6J male mice demonstrate significant in‐cage fighting compared to females, which introduces higher variation in their background mechanical loading.…”

Section: Discussionmentioning

confidence: 99%

“…During OA onset, traumatic damage results in abnormal mechanical loading on joints. Matrix‐embedded osteocytes sense mechanical alterations and orchestrate subchondral bone osteoclast differentiation and subsequent bone resorption through secretion of receptor activator of nuclear factor‐kappa B ligand (RANKL) 11 . Excessive activation of osteoclastogenesis and a rapid subchondral bone turnover result in subchondral bone resorption, frequently noticed before worn out cartilage during the development of OA 12 .…”

Section: Introductionmentioning

confidence: 99%

Farnesoid X receptor agonist attenuates subchondral bone osteoclast fusion and osteochondral pathologies of osteoarthritis via suppressing JNK1/2/NFATc1 pathway

Cai

Kang

et al. 2022

The FASEB Journal

View full text Add to dashboard Cite

Osteoarthritis (OA) is a prevalent degenerative disease of the joint, featured by articular cartilage destruction and subchondral bone marrow lesions. Articular cartilage and subchondral bone constitute an osteochondral unit that guarantees joint homeostasis. During OA initiation, activated osteoclasts in subchondral bone ultimately result in impaired capacities of the subchondral bone in response to mechanical stress, followed by the degradation of overlying articular cartilage. Thus, targeting osteoclasts could be a potential therapeutic option for treating OA. Here, we observed that farnesoid X receptor (FXR) expression and osteoclast fusion and activity in subchondral bone were concomitantly changed during early‐stage OA in the OA mouse model established by anterior cruciate ligament transection (ACLT). Then, we explored the therapeutic effects of FXR agonist GW4064 on the osteochondral pathologies in ACLT mice. We showed that GW4064 obviously ameliorated subchondral bone deterioration, associated with reduction in tartrate‐resistant acid phosphatase (TRAP) positive multinuclear osteoclast number, as well as articular cartilage degradation, which were blocked by the treatment with FXR antagonist Guggulsterone. Mechanistically, GW4064 impeded osteoclastogenesis through inhibiting subchondral bone osteoclast fusion via suppressing c‐Jun N‐terminal kinase (JNK) 1/2/nuclear factor of activated T‐cells 1 (NFATc1) pathway. Taken together, our results present evidence for the protective effects of GW4064 against OA by blunting osteoclast‐mediated aberrant subchondral bone loss and subsequent cartilage deterioration. Therefore, GW4064 demonstrates the potential as an alternative therapeutic option against OA for further drug development.

show abstract

Small Joint Organoids 3D Bioprinting: Construction Strategy and Application

Zhang,

Li,

Wang

et al. 2023

Small

View full text Add to dashboard Cite

Osteoarthritis (OA) is a chronic disease that causes pain and disability in adults, affecting ≈300 million people worldwide. It is caused by damage to cartilage, including cellular inflammation and destruction of the extracellular matrix (ECM), leading to limited self‐repairing ability due to the lack of blood vessels and nerves in the cartilage tissue. Organoid technology has emerged as a promising approach for cartilage repair, but constructing joint organoids with their complex structures and special mechanisms is still challenging. To overcome these boundaries, 3D bioprinting technology allows for the precise design of physiologically relevant joint organoids, including shape, structure, mechanical properties, cellular arrangement, and biological cues to mimic natural joint tissue. In this review, the authors will introduce the biological structure of joint tissues, summarize key procedures in 3D bioprinting for cartilage repair, and propose strategies for constructing joint organoids using 3D bioprinting. The authors also discuss the challenges of using joint organoids’ approaches and perspectives on their future applications, opening opportunities to model joint tissues and response to joint disease treatment.

show abstract

Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c-fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion

Cited by 45 publications

References 74 publications

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Farnesoid X receptor agonist attenuates subchondral bone osteoclast fusion and osteochondral pathologies of osteoarthritis via suppressing JNK1/2/NFATc1 pathway

Small Joint Organoids 3D Bioprinting: Construction Strategy and Application

Contact Info

Product

Resources

About