Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2-Immunometabolism-CSCIED科技核心评价数据库-手机版

Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2

Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2

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DOI	10.1097/IN9.0000000000000031
刊名	Immunometabolism IJ
年，卷(期)	2023, 5(4)
作者	Riggs, Keegan C.; Sankar, Uma,
作者单位	[Riggs, Keegan C.; Sankar, Uma] Indiana Univ Sch Med, Dept Anat Cell Biol & Physiol, Indianapolis, IN 46202 USA; [Riggs, Keegan C.; Sankar, Uma] Indiana Univ Sch Med, Indiana Ctr Musculoskeletal Hlth, Indianapolis, IN 46202 USA
摘要	Post-traumatic osteoarthritis (PTOA) is a multifactorial disease of the cartilage, synovium, and subchondral bone resulting from direct joint trauma and altered joint mechanics after traumatic injury. There are no current disease-modifying therapies for PTOA, and early surgical interventions focused on stabilizing the joint do not halt disease progression. Chronic pain and functional disability negatively affect the quality of life and take an economic toll on affected patients. While multiple mechanisms are at play in disease progression, joint inflammation is a key contributor. Impact-induced mitochondrial dysfunction and cell death or altered joint mechanics after trauma culminate in inflammatory cytokine release from synoviocytes and chondrocytes, cartilage catabolism, suppression of cartilage anabolism, synovitis, and subchondral bone disease, highlighting the complexity of the disease. Current understanding of the cellular and molecular mechanisms underlying the disease pathology has allowed for the investigation of a variety of therapeutic strategies that target unique apoptotic and/or inflammatory processes in the joint. This review provides a concise overview of the inflammatory and apoptotic mechanisms underlying PTOA pathogenesis and identifies potential therapeutic targets to mitigate disease progression. We highlight Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a serine/threonine protein kinase that was recently identified to play a role in murine and human osteoarthritis pathogenesis by coordinating chondrocyte inflammatory responses and apoptosis. Given its additional effects in regulating macrophage inflammatory signaling and bone remodeling, CaMKK2 emerges as a promising disease-modifying therapeutic target against PTOA.
Abstract	Post-traumatic osteoarthritis (PTOA) is a multifactorial disease of the cartilage, synovium, and subchondral bone resulting from direct joint trauma and altered joint mechanics after traumatic injury. There are no current disease-modifying therapies for PTOA, and early surgical interventions focused on stabilizing the joint do not halt disease progression. Chronic pain and functional disability negatively affect the quality of life and take an economic toll on affected patients. While multiple mechanisms are at play in disease progression, joint inflammation is a key contributor. Impact-induced mitochondrial dysfunction and cell death or altered joint mechanics after trauma culminate in inflammatory cytokine release from synoviocytes and chondrocytes, cartilage catabolism, suppression of cartilage anabolism, synovitis, and subchondral bone disease, highlighting the complexity of the disease. Current understanding of the cellular and molecular mechanisms underlying the disease pathology has allowed for the investigation of a variety of therapeutic strategies that target unique apoptotic and/or inflammatory processes in the joint. This review provides a concise overview of the inflammatory and apoptotic mechanisms underlying PTOA pathogenesis and identifies potential therapeutic targets to mitigate disease progression. We highlight Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a serine/threonine protein kinase that was recently identified to play a role in murine and human osteoarthritis pathogenesis by coordinating chondrocyte inflammatory responses and apoptosis. Given its additional effects in regulating macrophage inflammatory signaling and bone remodeling, CaMKK2 emerges as a promising disease-modifying therapeutic target against PTOA.
关键词	post-traumatic osteoarthritis; inflammation; chondrocytes; synovium; subchondral bone; Ca2+/calmodulin dependent protein kinase kinase 2
KeyWord	post-traumatic osteoarthritis; inflammation; chondrocytes; synovium; subchondral bone; Ca2+/calmodulin dependent protein kinase kinase 2
基金项目
页码	1-7

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引用本文

Riggs, Keegan C.; Sankar, Uma. Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2 [J]. Immunometabolism. 2023; 5; (4). 1 - 7.

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