2018
DOI: 10.18632/aging.101481
View full text |Buy / Rent full text
|
Sign up to set email alerts
|

Abstract: Progressive loss of tissue homeostasis is a hallmark of numerous age-related pathologies, including osteoarthritis (OA). Accumulation of senescent chondrocytes in joints contributes to the age-dependent cartilage loss of functions through the production of hypertrophy-associated catabolic matrix-remodeling enzymes and pro-inflammatory cytokines. Here, we evaluated the effects of the secreted variant of the anti-aging hormone α-Klotho on cartilage homeostasis during both cartilage formation and OA development. … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

4
21
0

Year Published

2019
2019
2020
2020

Publication Types

Select...
2
1

Relationship

0
3

Authors

Journals

citations
Cited by 18 publications
(85 citation statements)
references
References 47 publications
(85 reference statements)
4
21
0
Order By: Relevance
“…The Klotho enzyme is encoded by the human KL (mouse Kl ) gene; the gene product is a type-I membrane protein, related to β-glucuronidases; clinically, Klotho appears to improve cognition, kidney disease, and catabolic diseases of aging (reviewed in [81]). Because OA is correlated with increased hypertrophy-associated catabolic matrix-remodeling enzymes and pro-inflammatory cytokines, effects of Klotho were assessed in mouse cartilage homeostasis during both normal cartilage formation and development of OA; Kl expression was detected during embryonic limb development, and transiently during chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in culture [82]. Genome-wide transcriptomics of chondrocytes from OA patients revealed that incubation with recombinant-delivered Klotho repressed the expression of nitric-oxide synthase-2 ( NOS2 ) and the SLC39A8 / MMP13 catabolic-remodeling axis.…”
Section: Slc39a8 Clinical Studiesmentioning
confidence: 99%
“…In the AC of progeroid mice, we observed a statistically significant increase in Il1a, Il6, and Tnf-pro-inflammatory factors associated with the senescence-associated secretory phenotype (SASP)-compared to WT littermates ( Fig.1a). Gene expression of Mmp3, Mmp13, and Adamts5catabolic factors involved with cleaving ECM components such as collagen type II and aggrecans, [31,32] [33] were also significantly increased in Zmpste24 −/− progeroid mice (Fig. 1b).…”
Section: Articular Cartilage Of Progeroid Mice Shows Ageing-related Imentioning
confidence: 99%
“…α-Klotho acts as a co-receptor for FGF23 but was not required in this context; however, Chuchana et al . determined that treatment of human chondrocytes with recombinant α-Klotho or α-Klotho–targeting small interfering RNA (siRNA) suppressed or induced MMP13 expression, respectively 44 . The mechanism was not examined, but elsewhere α-Klotho is reported to disrupt signalling pathways, including Wnt, transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF) 44, 45 .…”
Section: Regulation By Mmp13 Transcriptionmentioning
confidence: 99%
“…determined that treatment of human chondrocytes with recombinant α-Klotho or α-Klotho–targeting small interfering RNA (siRNA) suppressed or induced MMP13 expression, respectively 44 . The mechanism was not examined, but elsewhere α-Klotho is reported to disrupt signalling pathways, including Wnt, transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF) 44, 45 . The authors suggest a chondroprotective role for α-Klotho in OA, although more detailed in vivo experiments are needed 44 .…”
Section: Regulation By Mmp13 Transcriptionmentioning
confidence: 99%
See 1 more Smart Citation