{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kotelsky A"],"funding":["NIAMS NIH HHS","NIGMS NIH HHS"],"pagination":["100227"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9718206"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(1)"],"pubmed_abstract":["<h4>Objective</h4>The objective of this study is to understand the role of altered <i>in vivo</i> mechanical environments in knee joints post anterior cruciate ligament (ACL)-injury in chondrocyte vulnerability against mechanical stimuli and in the progression of post-traumatic osteoarthritis (PT-OA).<h4>Methods</h4>Differential <i>in vivo</i> mechanical environments were induced by unilateral ACL-injury (uni-ACL-I) and bilateral ACL-injury (bi-ACL-I) in 8-week-old female C57BL/6 mice. The gait parameters, the mechano-vulnerability of <i>in situ</i> chondrocytes, Young's moduli of cartilage extracellular matrix (ECM), and the histological assessment of OA severity (OARSI score) were compared between control and experimental groups at 0∼8-weeks post-ACL-injury.<h4>Results</h4>We found that bi-ACL-I mice experience higher joint-loading on their both injured limbs, but uni-ACL-I mice balance their joint-loading between injured and uninjured hind limbs resulting in a reduced joint-loading during gait. We also found that at 4- and 8-week post-injury the higher weight-bearing hind limbs (i.e., bi-ACL-I) had the increased area of chondrocyte death induced by impact loading and higher OARSI score than the lower weight-bearing limbs (uni-ACL-I). Additionally, we found that at 8-weeks post-injury the ECM became stiffer in bi-ACL-I joints and softer in uni-ACL-I joints.<h4>Conclusions</h4>Our results show that ACL-injured limbs with lower <i>in vivo</i> joint-loading develops PT-OA significantly slower than injured limbs with higher joint-loading during gait. Our data also indicate that articular chondrocytes in severe PT-OA are more fragile from mechanical impacts than chondrocytes in healthy or mild PT-OA. Thus, preserving physiologic joint-loads on injured joints will reduce chondrocyte death post-injury and may delay PT-OA progression."],"journal":["Osteoarthritis and cartilage open"],"pubmed_title":["Effect of knee joint loading on chondrocyte mechano-vulnerability and severity of post-traumatic osteoarthritis induced by ACL-injury in mice."],"pmcid":["PMC9718206"],"funding_grant_id":["R01 AR082349","R35 GM147054"],"pubmed_authors":["Proctor A","Proschel C","Kotelsky A","Mannava S","Elahi A","Lee W","Nejat Yigit C"],"additional_accession":[]},"is_claimable":false,"name":"Effect of knee joint loading on chondrocyte mechano-vulnerability and severity of post-traumatic osteoarthritis induced by ACL-injury in mice.","description":"<h4>Objective</h4>The objective of this study is to understand the role of altered <i>in vivo</i> mechanical environments in knee joints post anterior cruciate ligament (ACL)-injury in chondrocyte vulnerability against mechanical stimuli and in the progression of post-traumatic osteoarthritis (PT-OA).<h4>Methods</h4>Differential <i>in vivo</i> mechanical environments were induced by unilateral ACL-injury (uni-ACL-I) and bilateral ACL-injury (bi-ACL-I) in 8-week-old female C57BL/6 mice. The gait parameters, the mechano-vulnerability of <i>in situ</i> chondrocytes, Young's moduli of cartilage extracellular matrix (ECM), and the histological assessment of OA severity (OARSI score) were compared between control and experimental groups at 0∼8-weeks post-ACL-injury.<h4>Results</h4>We found that bi-ACL-I mice experience higher joint-loading on their both injured limbs, but uni-ACL-I mice balance their joint-loading between injured and uninjured hind limbs resulting in a reduced joint-loading during gait. We also found that at 4- and 8-week post-injury the higher weight-bearing hind limbs (i.e., bi-ACL-I) had the increased area of chondrocyte death induced by impact loading and higher OARSI score than the lower weight-bearing limbs (uni-ACL-I). Additionally, we found that at 8-weeks post-injury the ECM became stiffer in bi-ACL-I joints and softer in uni-ACL-I joints.<h4>Conclusions</h4>Our results show that ACL-injured limbs with lower <i>in vivo</i> joint-loading develops PT-OA significantly slower than injured limbs with higher joint-loading during gait. Our data also indicate that articular chondrocytes in severe PT-OA are more fragile from mechanical impacts than chondrocytes in healthy or mild PT-OA. Thus, preserving physiologic joint-loads on injured joints will reduce chondrocyte death post-injury and may delay PT-OA progression.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-03-27T16:26:16.733Z","creation":"2025-04-05T19:45:16.849Z"},"accession":"S-EPMC9718206","cross_references":{"pubmed":["36474470"],"doi":["10.1016/j.ocarto.2021.100227"]}}