Targeting Cartilage Degradation in Osteoarthritis

McClurg, Oliver; Tinson, Ryan; Troeberg, Linda

doi:10.3390/ph14020126

Cited by 24 publications

(23 citation statements)

References 156 publications

(233 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The roles of FGF‐8 and FGFR in the development of normal cartilage tissue are manifested in the interaction in the dynamic balance of catabolism and anabolism 5,37–40 . In different stages of the growth and development of limbs and joints, different types of FGFRs successively bind to FGF‐8 to activate downstream signalling pathways with different intensities 8,41 …”

Section: Overview Of Fgf‐8 In Normal Cartilagementioning

confidence: 99%

“… 91,92 The early stages of osteoarthritis are characterized by the loss of the extracellular matrix 58 . In the normal articular cartilage matrix, the most important components are type II collagen fibres and aggrecans, and the synthesis and catabolism of type II collagen fibres and aggrecans maintain the dynamic balance and normal joint activities 38,65 . According to experimental results, syndecan‐4 gene (SDC4), which encodes syndecan‐4, is overexpressed in the cartilage of subjects with osteoarthritis, resulting in the overexpression of its downstream putative factor matrix metalloproteinase‐3 (MMP‐3) 85 …”

Section: The Relationship Between Fgf‐8 and Chondrocytes In Cartilage...mentioning

confidence: 99%

See 1 more Smart Citation

The role of fibroblast growth factor 8 in cartilage development and disease

Chen

Cui

Zhang

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

Fibroblast growth factor 8 (FGF‐8), also known as androgen‐induced growth factor (AIGF), is presumed to be a potent mitogenic cytokine that plays important roles in early embryonic development, brain formation and limb development. In the bone environment, FGF‐8 produced or received by chondrocyte precursor cells binds to fibroblast growth factor receptor (FGFR), causing different levels of activation of downstream signalling pathways, such as phospholipase C gamma (PLCγ)/Ca2+, RAS/mitogen‐activated protein kinase‐extracellular regulated protein kinases (RAS/MAPK‐MEK‐ERK), and Wnt‐β‐catenin‐Axin2 signalling, and ultimately controlling chondrocyte proliferation, differentiation, cell survival and migration. However, the molecular mechanism of FGF‐8 in normal or pathological cartilage remains unclear, and thus, FGF‐8 represents a novel exploratory target for studies of chondrocyte development and cartilage disease progression. In this review, studies assessing the relationship between FGF‐8 and chondrocytes that have been published in the past 5 years are systematically summarized to determine the probable mechanism and physiological effect of FGF‐8 on chondrocytes. Based on the existing research results, a therapeutic regimen targeting FGF‐8 is proposed to explore the possibility of treating chondrocyte‐related diseases.

show abstract

Section: Overview Of Fgf‐8 In Normal Cartilagementioning

confidence: 99%

Section: The Relationship Between Fgf‐8 and Chondrocytes In Cartilage...mentioning

confidence: 99%

The role of fibroblast growth factor 8 in cartilage development and disease

Chen

Cui

Zhang

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Genetic deletion of either leads to significant protection from joint damage in mice following surgical destabilization of the joint. Several pharmaceutical companies have developed aggrecanase inhibitors to attempt to treat OA (reviewed in [ 18 , 19 ]). Clinical trials in this area have largely failed, although the choice of primary clinical endpoints could be limiting the demonstration of efficacy in vivo.…”

Section: The Ecm In Osteoarthritis (Oa)mentioning

confidence: 99%

The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair

Vincent

McClurg

Troeberg

2022

IJMS

View full text Add to dashboard Cite

The extracellular matrix (ECM) has long been regarded as a packing material; supporting cells within the tissue and providing tensile strength and protection from mechanical stress. There is little surprise when one considers the dynamic nature of many of the individual proteins that contribute to the ECM, that we are beginning to appreciate a more nuanced role for the ECM in tissue homeostasis and disease. Articular cartilage is adapted to be able to perceive and respond to mechanical load. Indeed, physiological loads are essential to maintain cartilage thickness in a healthy joint and excessive mechanical stress is associated with the breakdown of the matrix that is seen in osteoarthritis (OA). Although the trigger by which increased mechanical stress drives catabolic pathways remains unknown, one mechanism by which cartilage responds to increased compressive load is by the release of growth factors that are sequestered in the pericellular matrix. These are heparan sulfate-bound growth factors that appear to be largely chondroprotective and displaced by an aggrecan-dependent sodium flux. Emerging evidence suggests that the released growth factors act in a coordinated fashion to drive cartilage repair. Thus, we are beginning to appreciate that the ECM is the key mechano-sensor and mechano-effector in cartilage, responsible for directing subsequent cellular events of relevance to joint health and disease.

show abstract

“…In the context of new therapeutic approaches emerging in the health system owing to the COVID-19 pandemic [12], and considering the increased burden of OA, existing promising treatments need to be refined and thoroughly elucidated in order to be adopted by the guidelines into the clinical practice. To this end, disease-modifying OA drugs [13][14][15], monoclonal antibodies [16,17] and autologous treatments such as chondrocyte implantation, mesenchymal stem cells and platelet-rich plasma comprise some alternative options [18]. However, since OA is a multifactorial disease with progressive development, it renders the aforementioned treatments limited in regards to the times that they can be employed [19] and the therapeutic impact that they may have.…”

Section: Introductionmentioning

confidence: 99%

Nutraceuticals for Knee Osteoarthritis Pain Relief. Results from a Preliminary Randomised Clinical Trial

et al. 2021

View full text Add to dashboard Cite

Osteoarthritis is the most common inflammation-based joint disease. Polyphenols are plant secondary metabolites with established antioxidant and anti-inflammatory properties. Recognizing the need for holistic approaches in the management of knee osteoarthritis, we designed a two-arm, randomised clinical trial to evaluate the efficacy of a supplement rich in phenolic compounds in OA. Primary outcomes included changes in Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale. Secondary outcome measures were the changes in WOMAC stiffness and functionality subscales. Patients were randomised (1:1) to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA). Μedical history, biochemical profile and anthropometric measurements were obtained. Eighty-six patients were screened and 25 were randomly allocated in a pilot study to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA) adjunct to stable medical treatment. The nutraceutical supplements were well tolerated and no adverse events were reported. VAS decreased in the PhAA group (p < 0.001). Additionally, WOMAC composite score decreased significantly only in the PhAA group (p < 0.05). The WOMAC subscale of pain decreased in both treatment groups (p = 0.001 for the PhAA group, p < 0.05 for the AA group). The decrease in the subscales of stiffness and physical function was not significant for either group. A possible improvement in the quality of life of these patients using nutraceutical supplements is apparent. Although preliminary, our positive results support the hypothesis that treatment with nutraceuticals may be effective for pain relief in osteoarthritis. ClinicalTrials.gov Identifier: NCT04783792.

show abstract

Targeting Cartilage Degradation in Osteoarthritis

Cited by 24 publications

References 156 publications

The role of fibroblast growth factor 8 in cartilage development and disease

The role of fibroblast growth factor 8 in cartilage development and disease

The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair

Nutraceuticals for Knee Osteoarthritis Pain Relief. Results from a Preliminary Randomised Clinical Trial

Contact Info

Product

Resources

About