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Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis.

Li X, Yang J, Liu D, Li J, Niu K, Feng S, Yokota H, Zhang P - Sci Rep (2016)

Bottom Line: Knee loading promotes bone formation, but its effects on OA have not been well investigated.Two weeks application of daily dynamic knee loading significantly reduced OARSI scores and CC/TAC (calcified cartilage to total articular cartilage), but increased SBP (subchondral bone plate) and B.Ar/T.Ar (trabecular bone area to total tissue area).Furthermore, knee loading exerted protective effects by suppressing osteoclastogenesis through Wnt signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

ABSTRACT
Osteoarthritis (OA) is a whole joint disorder that involves cartilage degradation and periarticular bone response. Changes of cartilage and subchondral bone are associated with development and activity of osteoclasts from subchondral bone. Knee loading promotes bone formation, but its effects on OA have not been well investigated. Here, we hypothesized that knee loading regulates subchondral bone remodeling by suppressing osteoclast development, and prevents degradation of cartilage through crosstalk of bone-cartilage in osteoarthritic mice. Surgery-induced mouse model of OA was used. Two weeks application of daily dynamic knee loading significantly reduced OARSI scores and CC/TAC (calcified cartilage to total articular cartilage), but increased SBP (subchondral bone plate) and B.Ar/T.Ar (trabecular bone area to total tissue area). Bone resorption of osteoclasts from subchondral bone and the differentiation of osteoclasts from bone marrow-derived cells were completely suppressed by knee loading. The osteoclast activity was positively correlated with OARSI scores and negatively correlated with SBP and B.Ar/T.Ar. Furthermore, knee loading exerted protective effects by suppressing osteoclastogenesis through Wnt signaling. Overall, osteoclast lineage is the hyper responsiveness of knee loading in osteoarthritic mice. Mechanical stimulation prevents OA-induced cartilage degeneration through crosstalk with subchondral bone. Knee loading might be a new potential therapy for osteoarthritis patients.

No MeSH data available.


Related in: MedlinePlus

The OA surgery and loading procedure, histological changes of articular cartilage and subchondral bone by H&E staining.(A,B) The medial collateral ligament was transected (Bar, 1 mm) and the medial meniscus was removed (Bar, 2 mm) on the right knee to induce osteoarthritis. Arrows indicated medial collateral ligament in A, and articular surfaces of femur and tibia in B. (C) Daily dynamic knee loading (1 N, 5 Hz) was applied at the right knee 5 min/day for 2 weeks. (D) H&E staining of tibial cartilage and subchondral bone plate (SBP). The thickness of hyaline cartilage (HC) and calcified cartilage (CC) were indicated by double arrows. Scale bar, 50 μm. (E) Quantitative analysis of the ratio of calcified cartilage to the total articular cartilage (CC/TAC). (F) Quantitative analysis of the thickness of subchondral bone plate (SBP). n = 10; **P < 0.01, ***P < 0.001.
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f1: The OA surgery and loading procedure, histological changes of articular cartilage and subchondral bone by H&E staining.(A,B) The medial collateral ligament was transected (Bar, 1 mm) and the medial meniscus was removed (Bar, 2 mm) on the right knee to induce osteoarthritis. Arrows indicated medial collateral ligament in A, and articular surfaces of femur and tibia in B. (C) Daily dynamic knee loading (1 N, 5 Hz) was applied at the right knee 5 min/day for 2 weeks. (D) H&E staining of tibial cartilage and subchondral bone plate (SBP). The thickness of hyaline cartilage (HC) and calcified cartilage (CC) were indicated by double arrows. Scale bar, 50 μm. (E) Quantitative analysis of the ratio of calcified cartilage to the total articular cartilage (CC/TAC). (F) Quantitative analysis of the thickness of subchondral bone plate (SBP). n = 10; **P < 0.01, ***P < 0.001.

Mentions: To examine the effect of knee loading on articular cartilage and subchondral bone in osteoarthritic mice, the medial collateral ligament (Fig. 1A, arrows) was transected and the medial meniscus (Fig. 1B, arrows showed the articular surfaces of femur and tibia) was removed on the right knee to induce osteoarthritis. Daily dynamic knee loading was applied at 1 N, 5 Hz, 5 min/day for 2 weeks (Fig. 1C). Alendronate (ALN), an anti-resorptive agent, was used as a positive control to evaluate the role of osteoclast activity in OA. The sections were stained with hematoxylin-eosin (H&E). The thickness of the calcified cartilage (CC) increased whereas the hyaline cartilage (HC) layer decreased with tidemark moving closer to articular surface in OA group. The calcified cartilage thickness was attenuated by ALN and loading treatment (Fig. 1D, black double arrows). The ratio of calcified cartilage to the total articular cartilage (CC/TAC) was examined to evaluate the changes of calcified cartilage and hyaline cartilage. Notably, the value of CC/TAC in the OA group was higher than in sham control, OA + ALN, and OA + loading groups (all P < 0.001; Fig. 1E). There is no significant difference between knee loading and ALN effect.


Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis.

Li X, Yang J, Liu D, Li J, Niu K, Feng S, Yokota H, Zhang P - Sci Rep (2016)

The OA surgery and loading procedure, histological changes of articular cartilage and subchondral bone by H&E staining.(A,B) The medial collateral ligament was transected (Bar, 1 mm) and the medial meniscus was removed (Bar, 2 mm) on the right knee to induce osteoarthritis. Arrows indicated medial collateral ligament in A, and articular surfaces of femur and tibia in B. (C) Daily dynamic knee loading (1 N, 5 Hz) was applied at the right knee 5 min/day for 2 weeks. (D) H&E staining of tibial cartilage and subchondral bone plate (SBP). The thickness of hyaline cartilage (HC) and calcified cartilage (CC) were indicated by double arrows. Scale bar, 50 μm. (E) Quantitative analysis of the ratio of calcified cartilage to the total articular cartilage (CC/TAC). (F) Quantitative analysis of the thickness of subchondral bone plate (SBP). n = 10; **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834538&req=5

f1: The OA surgery and loading procedure, histological changes of articular cartilage and subchondral bone by H&E staining.(A,B) The medial collateral ligament was transected (Bar, 1 mm) and the medial meniscus was removed (Bar, 2 mm) on the right knee to induce osteoarthritis. Arrows indicated medial collateral ligament in A, and articular surfaces of femur and tibia in B. (C) Daily dynamic knee loading (1 N, 5 Hz) was applied at the right knee 5 min/day for 2 weeks. (D) H&E staining of tibial cartilage and subchondral bone plate (SBP). The thickness of hyaline cartilage (HC) and calcified cartilage (CC) were indicated by double arrows. Scale bar, 50 μm. (E) Quantitative analysis of the ratio of calcified cartilage to the total articular cartilage (CC/TAC). (F) Quantitative analysis of the thickness of subchondral bone plate (SBP). n = 10; **P < 0.01, ***P < 0.001.
Mentions: To examine the effect of knee loading on articular cartilage and subchondral bone in osteoarthritic mice, the medial collateral ligament (Fig. 1A, arrows) was transected and the medial meniscus (Fig. 1B, arrows showed the articular surfaces of femur and tibia) was removed on the right knee to induce osteoarthritis. Daily dynamic knee loading was applied at 1 N, 5 Hz, 5 min/day for 2 weeks (Fig. 1C). Alendronate (ALN), an anti-resorptive agent, was used as a positive control to evaluate the role of osteoclast activity in OA. The sections were stained with hematoxylin-eosin (H&E). The thickness of the calcified cartilage (CC) increased whereas the hyaline cartilage (HC) layer decreased with tidemark moving closer to articular surface in OA group. The calcified cartilage thickness was attenuated by ALN and loading treatment (Fig. 1D, black double arrows). The ratio of calcified cartilage to the total articular cartilage (CC/TAC) was examined to evaluate the changes of calcified cartilage and hyaline cartilage. Notably, the value of CC/TAC in the OA group was higher than in sham control, OA + ALN, and OA + loading groups (all P < 0.001; Fig. 1E). There is no significant difference between knee loading and ALN effect.

Bottom Line: Knee loading promotes bone formation, but its effects on OA have not been well investigated.Two weeks application of daily dynamic knee loading significantly reduced OARSI scores and CC/TAC (calcified cartilage to total articular cartilage), but increased SBP (subchondral bone plate) and B.Ar/T.Ar (trabecular bone area to total tissue area).Furthermore, knee loading exerted protective effects by suppressing osteoclastogenesis through Wnt signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

ABSTRACT
Osteoarthritis (OA) is a whole joint disorder that involves cartilage degradation and periarticular bone response. Changes of cartilage and subchondral bone are associated with development and activity of osteoclasts from subchondral bone. Knee loading promotes bone formation, but its effects on OA have not been well investigated. Here, we hypothesized that knee loading regulates subchondral bone remodeling by suppressing osteoclast development, and prevents degradation of cartilage through crosstalk of bone-cartilage in osteoarthritic mice. Surgery-induced mouse model of OA was used. Two weeks application of daily dynamic knee loading significantly reduced OARSI scores and CC/TAC (calcified cartilage to total articular cartilage), but increased SBP (subchondral bone plate) and B.Ar/T.Ar (trabecular bone area to total tissue area). Bone resorption of osteoclasts from subchondral bone and the differentiation of osteoclasts from bone marrow-derived cells were completely suppressed by knee loading. The osteoclast activity was positively correlated with OARSI scores and negatively correlated with SBP and B.Ar/T.Ar. Furthermore, knee loading exerted protective effects by suppressing osteoclastogenesis through Wnt signaling. Overall, osteoclast lineage is the hyper responsiveness of knee loading in osteoarthritic mice. Mechanical stimulation prevents OA-induced cartilage degeneration through crosstalk with subchondral bone. Knee loading might be a new potential therapy for osteoarthritis patients.

No MeSH data available.


Related in: MedlinePlus