Loading‐Induced Reduction in Sclerostin as a Mechanism of Subchondral Bone Plate Sclerosis in Mouse Knee Joints During Late‐Stage Osteoarthritis

Abstract

Since focal stress on the SBP underlying sites of cartilage damage increases during late stages of OA, these findings establish mechanical loading-induced attenuation of sclerostin expression and elevation of bone formation along the SBP surface as the major mechanisms characterizing subchondral bone phenotypes associated with severe late-stage OA in mice.

Editorial: Wnt Signaling Related to Subchondral Bone Density and Cartilage Degradation in Osteoarthritis

“…The authors conclude that subchondral bone sclerosis occurs through a down‐regulation of sclerostin that is fueled by mechanical loading in those regions of the joint in which cartilage is breaking down . This is consistent with what we know about the role of sclerostin in mechanically induced bone formation from animal models involving in vivo mechanical loading of the joints .…”

“…As further evidence of this, they note that Sost ‐KO mice do not develop spontaneous cartilage deterioration, even in mature 14‐month‐old mice , despite the fact that down‐regulation of Sost results in a significant increase in bone volume and density . This is consistent with observations in human subjects, in individuals who have a gain‐of‐function mutation of the lipoprotein receptor–related protein 5 gene ( LRP5 ), which leads to high bone mass .…”

“…In the study by Jia et al in this issue of Arthritis & Rheumatology , the investigators examined the mechanisms of subchondral densification, and whether increased subchondral plate density is a sine qua non of progressive disease . Jia and colleagues employed several different mouse models for the study, and induced OA with 2 different surgical approaches.…”

Pros and cons of mouse models for studying osteoarthritis

“…They found SBP sclerosis primarily in areas underneath severely eroded articular cartilage. They also found a decrease in the levels of sclerostin in the SBP of mice with DMM induced OA [27]. Sclerostin is a small protein expressed by chondrocytes and osteocytes; it is not completely understood how reduced levels of sclerostin contribute to osteoarthritis but it is hypothesized that sclerostin prevents Wnt-pathway modulated expression of disintegrin and metalloproteinase [27].…”

“…Naturally occurring X X X X [9][10][11] Genetically modified X X X X [12][13][14][15][16][17][18][19][20][21][22][23][24] Surgically induced (all) X X X X X [25][26][27][28][29][30] Chemically induced (all) X [31][32][33][34][35][36][37][38][39] Non-invasive induction X X X X X [40][41][42][43][44][45][46][47][48][49][50][51][52] [5,8,63,64]…”