Related Experiment Video
Updated: Jun 1, 2026
Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants
Published on: January 7, 2019
Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis
B Y Chan1, E S Fuller, A K Russell
1Raymond Purves Bone and Joint Research Labs, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
Objectives:
To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation.
Methods:
SOST and other Wnt-β-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250 ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-β-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified.
Results:
Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-β-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro.
Conclusions:
These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.
Insights
Sclerostin (SOST) is expressed by cartilage cells in osteoarthritis and inhibits cartilage breakdown. However, SOST also promotes bone sclerosis, suggesting a dual role in osteoarthritis progression.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and subchondral bone changes.
- Sclerostin (SOST) is a protein primarily known for its role in bone metabolism, but its function in OA is not fully understood.
Purpose of the Study:
- To investigate the expression and regulation of SOST in articular cartilage during OA.
- To determine the effects of SOST on cartilage degradation and Wnt-β-catenin signaling in OA.
Main Methods:
- Immunolocalization of SOST and Wnt-β-catenin components in OA tissues (sheep, mice, human).
- In vitro studies on ovine chondrocytes to assess SOST expression regulation by inflammatory cytokines (IL-1α, TNFα).
- Assessment of recombinant SOST's effect on cartilage aggrecan degradation and chondrocyte gene expression.
Main Results:
- SOST is expressed by articular chondrocytes and upregulated by IL-1α in vitro.
- Chondrocyte SOST expression increases in damaged cartilage areas in OA models and human OA.
- SOST inhibits Wnt-β-catenin signaling and matrix metalloproteinase expression but also decreases matrix component synthesis; it dose-dependently inhibits IL-1α-induced aggrecanolysis.
Conclusions:
- SOST plays a complex role in OA, inhibiting cartilage degradation while promoting subchondral bone sclerosis.
- Targeting SOST may offer therapeutic potential for OA, but its dual effects need careful consideration.
Related Concept Videos
01:27Growth of Cartilage and Bone Tissue
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...