Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice

Lodewyckx, Liesbet; Cailotto, F.; Thysen, Sarah; Luyten, Frank P.; Lories, Rik

doi:10.1186/ar3695

Cited by 41 publications

(33 citation statements)

References 51 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lories et al [73] reported that the genetic association between osteoarthritis and FRZB polymorphisms is corroborated by increased cartilage proteoglycan loss in models of arthritis in Frzb(−/−) mice and loss of Frzb may contribute to cartilage damage by increasing the expression and activity of Mmps, in a Wnt-dependent and Wnt-independent manner. Consistent with this finding, Frzb knockout mice are more sensitive to chemical-induced OA [74]. …”

Section: Molecular Mechanisms Related To Oa Pathogenesismentioning

confidence: 54%

Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms

et al. 2014

View full text Add to dashboard Cite

Osteoarthritis (OA), the most prevalent chronic joint disease, increases in prevalence with age, and affects majority of individuals over the age of 65 and is a leading musculoskeletal cause of impaired mobility in the elderly. Because the precise molecular mechanisms which are involved in the degradation of cartilage matrix and development of OA are poorly understood and there are currently no effective interventions to decelerate the progression of OA or retard the irreversible degradation of cartilage except for total joint replacement surgery. In this paper, the important molecular mechanisms related to OA pathogenesis will be summarized and new insights into potential molecular targets for the prevention and treatment of OA will be provided.

show abstract

Section: Molecular Mechanisms Related To Oa Pathogenesismentioning

confidence: 54%

Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Moreover, protein secreted Frizzledrelated protein (Sfrp)3, a secreted negative regulatory factor of Wnt signaling, and mutations of the Frizzledrelated protein (FrzB) gene can increase susceptibility to OA (35). FrzB knockout mice are susceptible to chemical-induced OA (36). Furthermore, overexpression of Wnt-induced signaling protein 1 (WISP-1) in the mouse knee joint also leads to cartilage impairment.…”

Section: Effect Of Tgf-β In Articular Chondrocyte Degeneration In Oamentioning

confidence: 98%

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

Wei

Bai

2016

Connective Tissue Research

View full text Add to dashboard Cite

Osteoarthritis (OA), the most common form of degenerative joint disease, is linked to high morbidity. It is predicted to be the single greatest cause of disability in the general population by 2030. The development of disease-modifying therapy for OA currently face great obstacle mainly because the onset and development of the disease involve complex molecular mechanisms. In this review, we will comprehensively summarize biological and pathological mechanisms of three key aspects: degeneration of articular cartilage, synovial immunopathogenesis, and changes in subchondral bone. For each tissue, we will focus on the molecular receptors, cytokines, peptidases, related cell, and signal pathways. Agents that specifically block mechanisms involved in synovial inflammation, degeneration of articular cartilage, and subchondral bone remodeling can potentially be exploited to produce targeted therapy for OA. Such new comprehensive agents will benefit affected patients and bring exciting new hope for the treatment of OA.

show abstract

“…Indeed, transcriptomic analysis of the cartilage–subchondral bone unit in Frzb −/− mice revealed compensatory upregulation of other sFRPs, confirming that Wnt signalling in these tissues is tightly regulated. 64 …”

Section: Wnts and Oa: A Challenging Networkmentioning

confidence: 99%

To Wnt or not to Wnt: the bone and joint health dilemma

2013

View full text Add to dashboard Cite

The Wnt signalling cascades have essential roles in development, growth and homeostasis of joints and the skeleton. Progress in basic research, particularly relating to our understanding of intracellular signalling cascades and fine regulation of receptor activation in the extracellular space, has provided novel insights into the roles of Wnt signalling in chronic arthritis. Cartilage and bone homeostasis require finely tuned Wnt signalling; both activation and suppression of the Wnt–β-catenin cascade can lead to osteoarthritis in rodent models. Genetic associations with the Wnt antagonist encoded by FRZB and the transcriptional regulator encoded by DOT1L with osteoarthritis further corroborate the essential part played by Wnts in the joint. In rheumatoid arthritis, inhibition of Wnt signalling has a role in the persistence of bone erosions, whereas Wnts have been associated with the ankylosing phenotype in spondyloarthritis. Together, these observations identify the Wnt pathway as an attractive target for therapeutic intervention; however, the complexity of the Wnt signalling cascades and the potential secondary effects of drug interventions targeting them highlight the need for further research and suggest that our understanding of this exciting pathway is still in its infancy.

show abstract

Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice

Cited by 41 publications

References 51 publications

Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms

Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

To Wnt or not to Wnt: the bone and joint health dilemma

Contact Info

Product

Resources

About