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Mechanical stress suppressed miR-330 in the development of osteoarthritis and its protection from osteochondral degeneration

ABSTRACT: Abnormal mechanical stress plays a crucial role in the progression of osteoarthritis (OA). However, more key factors regulating mechanical response remain to be explored. This study harvested temporomandibular joint synovium fluids from 96 patients and revealed that miR-330 is significantly reduced under abnormal mechanical stress. Similarly, the expression of miR-330 is also decreased in cartilage and subchondral bone tissue from clinical specimen and animal models. Global knock out of miR-330 aggravated osteoarthritis development in both temporomandibular joint and knee joint. Conditional knock out of miR-330 in either chondrocytes or osteoclasts exhibited similar phenotype in both mechanical instable and aging animal models, suggesting the importance of miR-330 in both types of cells. Further molecular mechanism exploration unveiled that miR-330 can regulate the catabolism of chondrocytes and osteoclasts via suppressing CTGF, FGFR1 and EPOR as well as key inflammatory cytokines such as IL-1β and TNF-α. More importantly, intra-articular supplement of miR-330 exerts a therapeutic effect by mitigating the detrimental impacts of abnormal mechanical stress, where inhibition of chondrocytes apoptosis, osteoclasts activation and inflammation were further confirmed via single-cell RNA sequencing analysis. In conclusion, this study for the first time revealed that miR-330 is a mechanical responsive, osteoarthritis protective micro RNA. We provide evidence that miR-330 has potential diagnostic and therapeutic value for both temporomandibular and knee osteoarthritis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE307091 | GEO | 2026/06/11

REPOSITORIES: GEO

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Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.

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Mechanical stress suppressed miR-330 in the development of osteoarthritis and its protection from osteochondral degeneration

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