AI Article Synopsis
- Abnormal subchondral bone remodeling is crucial in osteoarthritis progression, with increased UCHL1 levels found in osteoclasts from OA patients.* -
- Deleting UCHL1 in osteoclast precursors worsens OA, while its overexpression helps reduce symptoms in male mice.* -
- The study reveals a new feedback loop involving RANKL, UCHL1, and soluble CD13 that controls osteoclast formation, suggesting a potential treatment target for OA.*
Article Abstract
Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466963 | PMC |
| http://dx.doi.org/10.1038/s41467-024-53119-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain.
Osteoarthr Cartil Open
March 2025
Pain Centre Versus Arthritis and Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, UK.
Objectives: Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.
Methods: Rats (n = 8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery.
[Therapeutic effect of joint injection of platelet-rich plasma combined with shock wave on osteochondral injury of talus].
Zhongguo Gu Shang
December 2024
Department of Radiology, Sichuan Orthopaedic Hospital, Chengdu 610041, Sichuan, China.
Objective: To explore clinical efficacy of platelet rich plasma (PRP) injection combined with extracorporeal shock wave therapy (ESWT) in treating osteochondral lesion of talus (OLT) with typeⅡa.
Methods: From January 2022 to June 2022, 45 patients with typeⅡa OLT were treated with PRP arthroscopic injection combined with ESWT, including 29 males and 16 females; aged from 18 to 63 years old with an average of(37.7±10.
A vascularized microfluidic model of the osteochondral unit for modeling inflammatory response and therapeutic screening.
Lab Chip
December 2024
CFD Research Corporation, 6820 Moquin Dr. N.W., Huntsville, AL 35806, USA.
Osteoarthritis (OA) has long been considered a disease of the articular cartilage. Within the past decade it has become increasingly clear that OA is a disease of the entire joint space and that interactions between articular cartilage and subchondral bone likely play an important role in the disease. Driven by this knowledge, we have created a novel microphysiological model of the osteochondral unit containing synovium, cartilage, bone, and vasculature in separate compartments with molecular and direct cell-cell interaction between the cells from the different tissue types.
View Article and Find Full Text PDFControlled Release of Human Dental Pulp Stem Cell-Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis.
Adv Healthc Mater
December 2024
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell-derived exosomes, which have anti-inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA.
View Article and Find Full Text PDFAll Arthroscopic Osteochondral Autograft Transplantation for Medial Talar Dome Lesions Talus With Burring of the Anterior Lip of the Distal Tibia.
Arthrosc Tech
November 2024
Orthopaedic Department, Faculty of Medicine in Assiut, Al-Azhar University, Cairo, Egypt.
Osteochondral lesions of the talus are chondral lesions affecting the subchondral bone mostly due to acute ankle trauma, including either sprains or fractures. After failure of conservative treatment, operative treatment is necessary, with different surgical techniques described in the literature. We describe a single-step osteochondral autograft transfer to access the medial talar dome lesion that avoids the need for a medial malleolar osteotomy and therefore eliminates morbidity while reducing operative time.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!