Aging processes and the development of osteoarthritis

Loeser, Richard F.

doi:10.1097/bor.0b013e32835a9428

Cited by 227 publications

(203 citation statements)

References 37 publications

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“…Age‐associated changes occur in many of the cells and tissues of the joint, which together play an active role in the development of OA through mechanisms such as the propagation of inflammatory cascades (Loeser, 2013). Of particular relevance is the recent finding that osteocytes exhibit features of cellular senescence with age, including expression of p16 INK4a and SASP markers (Farr et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

et al. 2018

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SummaryCellular senescence drives a functional decline of numerous tissues with aging by limiting regenerative proliferation and/or by producing pro‐inflammatory molecules known as the senescence‐associated secretory phenotype (SASP). The senescence biomarker p16 INK 4a is a potent inhibitor of the cell cycle but is not essential for SASP production. Thus, it is unclear whether p16 INK 4a identifies senescence in hyporeplicative cells such as articular chondrocytes and whether p16 INK 4a contributes to pathologic characteristics of cartilage aging. To address these questions, we examined the role of p16 INK 4a in murine and human models of chondrocyte aging. We observed that p16 INK 4a mRNA expression was significantly upregulated with chronological aging in murine cartilage (~50‐fold from 4 to 18 months of age) and in primary human chondrocytes from 57 cadaveric donors (r 2 = .27, p < .0001). Human chondrocytes exhibited substantial replicative potential in vitro that depended on the activity of cyclin‐dependent kinases 4 or 6 (CDK4/6), and proliferation was reduced in cells from older donors with increased p16 INK 4a expression. Moreover, increased chondrocyte p16 INK 4a expression correlated with several SASP transcripts. Despite the relationship between p16 INK 4a expression and these features of senescence, somatic inactivation of p16 INK 4a in chondrocytes of adult mice did not mitigate SASP expression and did not alter the rate of osteoarthritis (OA) with physiological aging or after destabilization of the medial meniscus. These results establish that p16 INK 4a expression is a biomarker of dysfunctional chondrocytes, but that the effects of chondrocyte senescence on OA are more likely driven by production of SASP molecules than by loss of chondrocyte replicative function.

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Section: Discussionmentioning

confidence: 99%

Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

et al. 2018

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“…Both articular cartilage and meniscal tissue are subject to degeneration (aging), with a declining synthesis capacity mainly of collagen and decreased numbers of fibrocytes (apoptosis), which are associated with decreased biomechanical resistance [22,31,48]. Thus, such alterations to the medial meniscus are present in more than half of patients after age 50, while those to the lateral meniscus are present in approximately 25% of patients [13,15].…”

Section: Introductionmentioning

confidence: 99%

The frequency of cartilage lesions in non-injured knees with symptomatic meniscus tears: results from an arthroscopic and NIR- (near-infrared) spectroscopic investigation

Spahn¹,

Plettenberg²,

Hoffmann³

et al. 2017

Arch Orthop Trauma Surg

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Through our investigations, a high, if not complete, concomitance of degenerative cartilage lesions and degenerative meniscus damage was demonstrated. From this it can be concluded that the entity of "isolated degenerative meniscus damage" clearly does not exist in practice. It is therefore highly probable that degenerative meniscus lesions, as a part of general joint degeneration, are to be interpreted in the context of the development of arthrosis. The practical consequences still are unclear. Patients after partial meniscectomy need a longer follow-up to detect potential cartilage lesions as well as an OA progression.

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“…Aging and OA are often inextricably linked, 9,10 and it is important to understand 574838C ARXXX10.1177/1947603515574838CartilageBrady et al …”

Section: Introductionmentioning

confidence: 99%

Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis

2015

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Chondrogenic progenitor populations, including mesenchymal stem cells, represent promising cell-based transplantation or tissue engineering therapies for the regeneration of damaged cartilage. Osteoarthritis (OA) predominantly affects the elderly and is a leading cause of disability worldwide. Advancing age is a prominent risk factor that is closely associated with the onset and progression of the disease. Understanding the influence that aging and OA have on chondrogenic progenitor cells is important to determine how these processes affect the cellular mechanisms of the cells and their capacity to differentiate into functional chondrocytes for use in therapeutic applications. Here, we review the effect of age-and OA-related changes on the growth kinetics and differentiation potential of chondrogenic progenitor cell populations. Aging differentially influences the proliferative potential of progenitor cells showing reduced growth rates with increased senescence and apoptotic activity over time, while chondrogenesis appears to be independent of donor age. Cartilage tissue affected by OA shows evidence of progenitor populations with some potential for repair, however reports on the proliferative propensity of mesenchymal stem cells and their chondrogenic potential are contradictory. This is likely attributed to the narrow age ranges of samples assessed and deficits in definitively identifying donors with OA versus healthy patients across a wide scope of advancing ages. Further studies that investigate the mechanistic effects of chondrogenic progenitor populations associated with aging and the progression of OA using clearly defined criteria and age-matched control subject groups are crucial to our understanding of the clinical relevance of these cells for use in cartilage repair therapies.

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Aging processes and the development of osteoarthritis

Cited by 227 publications

References 37 publications

Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

The frequency of cartilage lesions in non-injured knees with symptomatic meniscus tears: results from an arthroscopic and NIR- (near-infrared) spectroscopic investigation

Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis

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Aging processes and the development of osteoarthritis

Cited by 227 publications

References 37 publications

Expression of p16INK4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

Expression of p16INK4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

The frequency of cartilage lesions in non-injured knees with symptomatic meniscus tears: results from an arthroscopic and NIR- (near-infrared) spectroscopic investigation

Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis

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Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

Expression of p16^INK^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis