Publisher Correction: Accelerating functional gene discovery in osteoarthritis

Butterfield, Natalie C.; Curry, Katherine F; Steinberg, Julia; Dewhurst, Hannah; Komla-Ebri, Davide; Mannan, Naila S.; Adoum, Anne‐Tounsia; Leitch, Victoria; Logan, John G.; Waung, Julian A.; Ghirardello, Elena J.; Southam, Lorraine; Youlten, Scott E.; Wilkinson, J. Mark; McAninch, Elizabeth A.; Vancollie, Valerie E.; Kussy, Fiona; White, Jacqueline K.; Lelliott, Christopher J.; Adams, David J.; Jacques, Richard; Bianco, Antonio C.; Boyde, A.; Zeggini, Eleftheria; Croucher, Peter I.; Williams, Graham R.; Bassett, J. H. Duncan

doi:10.1038/s41467-021-23768-8

Cited by 7 publications

(8 citation statements)

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“…These categories coming from a population-based study are not only an epidemiologic structure but may also help clinicians to implement diagnostic and therapeutic procedures, advanced care planning, and assign resources to older adult in the entire functional continuum, starting from normal function (category 4) to functional decline (categories 2 and 5), and then to disability (categories 1 and 3). Since disability is a common end-result of acute and chronic conditions in the older population [ 44 , 45 ], the new classification could help solve the always difficult decision process around when to screen and take the subsequent interventions for osteoarthritis [ 46 ], depression [ 47 ], adverse events [ 48 ] and a major predictor to the years to survive, which now is age-determined. Other procedures that could benefit from the use of the new classification in the treatment decision-making process might be heart failure, chronic kidney disease, among others.…”

Section: Discussionmentioning

confidence: 99%

Novel subgroups of functional ability in older adults and their associations with adverse outcomes

Han

Zhang

2022

BMC Geriatr

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Background There is no general agreement on a standard form of functional classification in older adults and is mainly assessed by Activities of Daily Living (ADL) and/or Instrument Activity of Daily Living. A refined classification based on evaluation the limitations of intrinsic capacity, environment and social interaction, could provide a basis to predict the future disability and identify individuals with increased risk of adverse outcomes. Methods A new functional classification among older adults aged 60 and over was conducted by latent class analysis and compared with the traditional classifications, based on the China Health and Retirement Longitudinal Study. To further investigate the scientific validity of this new classification, associations with 7-year mortality and ADLs impairments among categories were tested by using Survival curves and Cox proportional hazard models. This was followed by the confirmatory analysis related to the prospective data. Competing risk analysis was also performed to analysis the sensitivity to further support our conclusions. Results Five categories were identified among 5,992 older adults which gave the best fitting, yielding a significant Bootstrap Likelihood Ratio Test (p < 0.001) and Lo-Mendell-Rubin adjusted likelihood ratio test (p < 0.001), with an entropy over 0.80. The presence of five categories: “health” (34.0%), “sub-disorder status” (36.6%), “acute diseases” (10.3%), “somatic functional disorder” (7.7%), and “viability disorder” (11.4%), which matched well with the functional independence rates by the international classifications. Among them, those in “sub-disorder status” were considered as an intermediate status between disability and health. The findings also revealed that those who were in “acute disease”, “somatic functional disorders”, “health” and “sub-disorder status” had a significant lower risk of mortality and ADLs limitations than “viability disorder”. And the risks gradually increased towards the less functionally independent end of the classification. However, the distribution of characteristics among five categories were in a synchronous change, indicating a stable classification. Conclusions A new classification representing the functional heterogeneity of older adults could effectively stratify the risk of mortality and ADLs limitations. Identifying the clusters of functional decline might be useful in predicting subsequent ageing trends, designing personalized intervention, and delaying the progression of disability and preventing its occurrence.

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Section: Discussionmentioning

confidence: 99%

Novel subgroups of functional ability in older adults and their associations with adverse outcomes

Han

Zhang

2022

BMC Geriatr

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“…Reduced expression of PITX1 protein promotes subchondral bone thickness and is involved in OA pathogenesis. A detailed study in humans on gene expression shows that Ccd6, Col4a2, Arhgap30, Gsdme, Unk, Josd1plays a crucial role in the pathogenesis of OA (133).…”

Section: Dysregulation Of Vascular Niches In Osteoarthritismentioning

confidence: 99%

Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases

et al. 2021

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The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.

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“…Primary osteoarthritis (OA) is the most common cause of knee arthritis worldwide 1 . OA leads to chronic disability due to pain and joint dysfunction 2 . Joint replacement for end-stage OA remains the only remedy, leading to an escalating healthcare problem in our obese and ageing society 3 .…”

Section: Introductionmentioning

confidence: 99%

“…Joint replacement for end-stage OA remains the only remedy, leading to an escalating healthcare problem in our obese and ageing society 3 . OA is characterized by articular cartilage damage and loss, together with structural abnormalities of subchondral bone and low-grade chronic joint inflammation 2 , 4 . There are no effective treatments to prevent the progression of OA.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation

Xu,

Furbish

et al. 2024

Commun Biol

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Osteoarthritis (OA) is one of the leading causes of disability, affecting over 500 million adults worldwide. Previous studies have found that various inflammatory factors can contribute to the pathogenesis of OA, including complement factors in the synovial fluid of OA patients. However, the pathogenesis of this disease is still not known, and the only therapy of severe OA is total joint replacements. Total joint replacements are invasive, expensive, and affect quality of life. Here we show that when human articular chondrocytes are stimulated with pro-inflammatory mediator interleukin-1β (IL-1β) there is an increase in inflammatory factors including complement component 3 (C3). We also found the transcription factor, signal transducer and activator of transcription 1 (STAT1), is responsible for increased C3 expression after IL-1β stimulation in human articular chondrocytes. A specific STAT1 inhibitor, fludarabine, attenuates the hyper-expression of C3 and delays/prevents spontaneous OA in Dunkin-Hartley guinea pigs. Since fludarabine is already clinically used for chemotherapy, this study has great translational potential as a unique disease-modifying osteoarthritis drug (DMOAD) in treating primary OA.

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Publisher Correction: Accelerating functional gene discovery in osteoarthritis

Abstract: The original version of this Article contained private information in the Data Availability statement, which was used by reviewers to access Proteomics datasets. This information has now been removed from both the PDF and HTML versions of this article.

Cited by 7 publications

References 0 publications

Novel subgroups of functional ability in older adults and their associations with adverse outcomes

Novel subgroups of functional ability in older adults and their associations with adverse outcomes

Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases

Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation

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