Senescence in osteoarthritis: from mechanism to potential treatment

Abstract

Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of senescent chondrocytes are found in OA cartilage. Selective clearance of senescent chondrocytes in a post-traumatic osteoarthritis (PTOA) mouse model ameliorated OA development, while intraarticular injection of senescent cells induced mouse OA. However, the means and extent to which senescence affects OA remain unclear. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. A relatively comprehensive discussion is presented in that section. Risk factors for OA are ageing, obesity, metabolic disorders and mechanical overload. Determining the relationship between known risk factors and senescence will help elucidate OA pathogenesis and identify optimal treatments.

Correlation between the Signal Intensity Alteration of Infrapatellar Fat Pad and Knee Osteoarthritis: A Retrospective, Cross-Sectional Study

“…Advanced age is regarded as a separate risk factor for osteoarthritis [ 49 ]. At first, it was found that senescent chondrocytes increased in osteoarthritis patients.…”

Perinatal mesenchymal stromal cells of the human decidua restore continence in rats with stress urinary incontinence induced by simulated birth trauma and regulate senescence of fibroblasts from women with stress urinary incontinence

“…Upregulation of IL-8, VEGF, MCP-1, MCP-2, or MCP-3 has been found in the female genitourinary tract immediately after VD (Wood et al, 2008). These cytokines and chemokines are secreted in inflammatory processes, but they are also part of what is known as SASP or senescence-associated secretory phenotype (Coppe et al, 2010;Lopes-Paciencia et al, 2019). SUI, as other pelvic floor disorders, is not considered an inflammatory disease but rather a multifactorial chronic disorder related to tissue deterioration.…”

“…Closely associated with cellular senescence is ECM remodeling, a process with consequences on tissue homeostasis. These phenomena feed off each other since some of the molecules that make up the SASP are MMPs or enzymes that degrade the ECM (Coppe et al, 2010;Lopes-Paciencia et al, 2019), and abnormal ECM remodeling is thought to lead to cellular senescence (Blokland et al, 2020). There is also in vivo data on the implication of ECM-degrading enzymes in incontinence, as increased MMP-2 and MMP-9 activity was reported in the vaginal wall after VD (Rahn et al, 2008).…”

“…Based on our observations regarding SUI cells behavior in culture we agree with other authors that cellular senescence may be one of the main pathological mechanisms underlying SUI ( Alperin et al, 2022 ). Cellular senescence is a process that can be caused by mechanical stress ( Liu et al, 2022 ), oxidative stress ( Del Rey et al, 2019 ) or estrogen depletion ( Wei et al, 2021 ), among others, and contributes to tissue aging since senescent cells negatively affect nearby cells and surrounding tissues through paracrine mechanisms. To our knowledge, this is the first demonstration of cellular senescence mechanisms associated with SUI.…”

Therapy free of cells vs human mesenchymal stem cells from umbilical cord stroma to treat the inflammation in OA

“…Osteoarthritis (OA) is the most common joint disease and a degenerative disease. The accumulation of senescent cells in the cartilage is implicated in the development of this pathology [3]. The senescent cells have a senescenceassociated secretory phenotype (SASP) implicated in the intercellular communication between cells [4].…”