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. 2023 Aug 17;18(8):e0270074.
doi: 10.1371/journal.pone.0270074. eCollection 2023.

Low-frequency whole-body vibration can enhance cartilage degradation with slight changes in subchondral bone in mice with knee osteoarthritis and does not have any morphologic effect on normal joints

Affiliations

Low-frequency whole-body vibration can enhance cartilage degradation with slight changes in subchondral bone in mice with knee osteoarthritis and does not have any morphologic effect on normal joints

Haiming Wang et al. PLoS One. .

Abstract

Purposes: To evaluate the effects of low frequency whole-body vibration (WBV) on degeneration of articular cartilage and subchondral bone in mice with destabilization of the medial meniscus (DMM)induced osteoarthritis(OA) and mice with normal knee.

Methods: Ten-week-old C57BL/6J male mice received DMM on right knees, while the left knees performed sham operation. There were six groups: DMM, SHAM DMM, DMM+WBV,SHAM DMM+WBV, DMM+ NON-WBV and SHAM DMM+NON-WBV. After four weeks, the knees were harvested from the DMM and SHAM DMM group. The remaining groups were treated with WBV (10 Hz) or NON-WBV. Four weeks later, the knees were harvested. Genes, containing Aggrecan(Acan) and CollagenⅡ(Col2a1), Matrix Metalloproteinases 3 and 13(MMP3,13), TNFα and IL6, were measured and staining was also performed. OA was graded with OARSI scores, and tibial plateaubone volume to tissue volume ratio(BV/TV), bone surface area to bone volume ratio (BS/BV), trabecular number(Tb.N) and trabecular thickness separation(TS) between groups were analyzed.

Results: Increased OARSI scores and cartilage degradation were observed after WBV. BV/TV, Tb.N and TS were not significant between the groups. Significant reductions were observed in MMP3, MMP13, Col2a1, Acan, TNFα and IL6 in the DMM+WBV compared to SHAM DMM+WBV group. BV/TV, BS/BV, Tb.N, TS and OARSI scores were not significantly changed in the left knees. IL6 expression in the SHAM DMM+WBV group was significantly increased compared with the SHAM DMM+ NON-WBV group, while Col2a1, Acan and MMP13 expression decreased.

Conclusion: WBV accelerated cartilage degeneration and caused slight changes in subchondral bone in a DMM-induced OA model. WBV had no morphologic effect on normal joints.

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Conflict of interest statement

The authors have declared that no competing interests exist

Figures

Fig 1
Fig 1. Analysis of the changes in diameter of knee joint following WBV.
(A) WBV induced weight loss in the mouse model of OA and no weight changes in the normal mice (n = 12). (B) Representative knee joint samples with the complete capsule retained, dissected free from muscles and ligaments. (C) Joint hypertrophy in the groups underwent DMM surgery than the sham operation groups (n = 6). Data are expressed as the mean ± SD. *P<0.05,**P<0.01.
Fig 2
Fig 2. Histologic appearance of the mouse joints after exposure to WBV.
(A) Representative coronal sections of the knee joint, stained with Safranin O/fast green from the mice, exposed to WBV for 4 weeks and the untreated sham controls. Images are oriented with the femoral condyle on top, and the tibial plateau on the bottom. Damage to cartilage was detected within the joint in all the mice that underwent DMM surgery, regardless of whether they were exposed to 4 weeks of WBV. The mouse model of OA exposed to WBV showed more severely deteriorated cartilage than the OA model with sham WBV. No obvious damage was detected in the control mice with sham DMM. (B) Knee joints were scored using the OARSI scoring system to quantify the degree of joint degeneration, and the mean maximum OARSI scores are presented corresponding to the medial articular surface. The mice exposed to 4 weeks of WBV had obvious degeneration, compared with the mice in the sham DMM group and DMM group that were age-matched and not treated with WBV.(n = 6). Data are expressed as the mean ± SD.*P<0.05,**P<0.01.
Fig 3
Fig 3. Analysis of tibial subchondral bone microarchitecture after WBV.
(I) Representative coronal and sagittal micro-CT images of the knee joint (A, B). ROI (the green region) defined from the tibial growth plate to the tibial plateau (C,D).Three-dimensional reconstruction of the whole knee joint (E, F). (II) Morphometric analysis of the subchondral bone in all groups, with or without WBV, shows no significant change in the bone microstructure parameters, including bone volume to tissue volume ratio (BV/TV), bone surface area to bone volume ratio (BS/BV), trabecular number (Tb. N) and trabecular thickness separation (TS) in all the groups, except OA group exposed to WBV compared to the matched control group with sham DMM.(n = 6).Data are expressed as the mean ± SD.*P<0.05.
Fig 4
Fig 4. Relative mRNA expression levels of Acan, Col2a1, MMP3, MMP13, TNFα and IL6 in the knee joint cartilage.
Compared to the baseline group with sham DMM, the group that underwent DMM surgery exhibited an obvious increase in Acan, Col2a1, MMP3 and MMP13. The mouse model of OA eight weeks after surgery showed a further increase in MMP3 and MMP13, while Acan and Col2a1 showed a decrease, compared with those of the baseline OA group. Obvious increases in TNFα and IL6 were also presented in the mouse model of eight weeks after surgery compared to those in the matched group four weeks after DMM surgery. All the genes detected had a significant decrease in the group with OA and WBV compared with the non-vibrated group. (n = 6). Data are expressed as the mean ± SD.**P<0.01.
Fig 5
Fig 5. Immunohistochemistry staining for Col2a1, Acan, MMP3, MMP13, IL6 and TNFα in the knee joint cartilage.
Compared to the baseline group with sham DMM, the group that underwent DMM surgery exhibited an obvious decrease in Acan and Col2a1, and increase in MMP3, MMP13, IL6 and TNFα. The mouse model of OA eight weeks after surgery showed a further increase in MMP3, MMP13, and an obivious decrease in Acan, Col2a1, compared with those of the baseline OA group. All the proteins detected had a significant decrease in the group DMM+WBV compared with the DMM+NON-WBV group. (n = 6).

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Grants and funding

The National Natural Science Foundation of China (Grant No. 81572231, 81972146) and the Project of the Science and Technology Department in Sichuan province (Grant No. 2019YJ0119). Sichuan Provincial Department of Science and Technology Fund (2021YJ0463, 2021YFS0070). The Project of the Science and Technology Department in Henan Provincial Department (Grant No. 22170112). The Joint project of Henan Provincial Health Commission (Grant No.LHGJ 20190252).The Natural Science Foundation of China-Henan Province (Grant No. 202300410388). Key Research Projects of Higher Education Institutions in Henan Province(Grant No. 21A320041). Henan Medical Education Research Project (Grant No. Wjlx2020529).
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