Axial alignment is a critical regulator of knee osteoarthritis

Abstract

Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion. Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.

Subchondral bone remodeling patterns in larger animal models of meniscal injuries inducing knee osteoarthritis – a systematic review

“…A detailed systematic review analyzed meniscectomy-induced OA in sheep [ 50 ], although the focus was not on subchondral bone alterations and no studies before 2010 were reported. Surgical OA induction was achieved via total medial (n = 2 studies) [ 3 , 12 ], total lateral (n = 3 studies) [ 11 , 13 , 29 ], and anterior partial medial (n = 2 studies) [ 43 , 44 ] meniscectomy, complete transection of the medial pars intermedia (i.e. MMT; n = 1 study) [ 12 ], and DMM (n = 1 study) [ 12 ] (Table 6 ).…”

A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo

“…[ 51,52 ] For the evaluation of the 3D microstructure of the subchondral bone, CT Analyzer software version 1.18 (Bruker) was used. In the osteochondral unit of each defect standardized volumes of interest (VOI) were defined to separate the “subchondral bone plate” and “subarticular spongiosa.” [ 52,53 ] VOIs had no intersections. Similar VOIs of the normal osteochondral unit were also examined in each trochlea, adjacent to the defects but not overlapping with them.…”

“…Multivariate analyses were performed for all available bone or cartilage parameters of the samples as described previously. [52][53][54]56] Principal components analysis (PCA) with a correlation matrix routine, and non-parametric one-way analysis of similarities (ANOSIM) with Gower similarity index were used, and considering multiplicity issues, the Bonferroni-corrected p-values were reported. [57] Calculations were performed using GraphPad Prism 7.03 (GraphPad Software, San Diego, CA, USA) or Past v. 4.04.…”

Beyond Traditional Medicine: EVs-Loaded Hydrogels as a Game Changer in Disease Therapeutics

“…In addition, the articular cartilage cannot repair itself, and once damaged, it will continue to deteriorate [ 126 ]. OA is the leading cause of disability worldwide [ 127 , 128 ]. The role and mechanism of articular chondrocytes (ACs) and BMSCs in cartilage repair have been extensively studied [ 129 , 130 , 131 ], and their mechanisms of action typically involve EVs.…”