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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

Effects of knee loading on gene expression in a mouse model of osteoarthritis.(A,B) Immunohistochemistry staining of Wnt3a and NFATc1 in sagittal sections of tibial cartilage were conducted (Bar = 50 μm). (C,D) Quantification of Wnt3a and NFATc1-positive cells in tibial cartilage were examined. n = 10. (E) Western blot analysis of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K in OA treated with knee loading. Cropped blots were used in the figure. Full-length blots were presented in Supplementary Fig. S2. (F) Relative mRNA levels of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K. n = 6; *P < 0.05, **P < 0.01, ***P < 0.001.
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f6: Effects of knee loading on gene expression in a mouse model of osteoarthritis.(A,B) Immunohistochemistry staining of Wnt3a and NFATc1 in sagittal sections of tibial cartilage were conducted (Bar = 50 μm). (C,D) Quantification of Wnt3a and NFATc1-positive cells in tibial cartilage were examined. n = 10. (E) Western blot analysis of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K in OA treated with knee loading. Cropped blots were used in the figure. Full-length blots were presented in Supplementary Fig. S2. (F) Relative mRNA levels of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K. n = 6; *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: To evaluate the mechanism of knee loading effect on OA at the molecular level, we examined the activities of Wnt3a, together with NFATc1, RANKL, TNF-α, and Cathepsin K in the tibia. Immunohistochemistry staining of Wnt3a and NFATc1 further validated the effects of knee loading on promotion of Wnt3a and inhibition of NFATc1 in cartilage cells (Fig. 6A–D). Both western blot analysis and quantitative real-time PCR of proximal tibia showed that the expression of Wnt3a was significantly increased by knee loading. However, the protein and mRNA levels of NFATc1, RANKL, TNF-α, and Cathepsin K were significantly suppressed by knee loading (Fig. 6E,F and Supplementary Fig. S2).


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)

Effects of knee loading on gene expression in a mouse model of osteoarthritis.(A,B) Immunohistochemistry staining of Wnt3a and NFATc1 in sagittal sections of tibial cartilage were conducted (Bar = 50 μm). (C,D) Quantification of Wnt3a and NFATc1-positive cells in tibial cartilage were examined. n = 10. (E) Western blot analysis of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K in OA treated with knee loading. Cropped blots were used in the figure. Full-length blots were presented in Supplementary Fig. S2. (F) Relative mRNA levels of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K. n = 6; *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Effects of knee loading on gene expression in a mouse model of osteoarthritis.(A,B) Immunohistochemistry staining of Wnt3a and NFATc1 in sagittal sections of tibial cartilage were conducted (Bar = 50 μm). (C,D) Quantification of Wnt3a and NFATc1-positive cells in tibial cartilage were examined. n = 10. (E) Western blot analysis of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K in OA treated with knee loading. Cropped blots were used in the figure. Full-length blots were presented in Supplementary Fig. S2. (F) Relative mRNA levels of Wnt3a, NFATc1, RANKL, TNF-α, and Cathepsin K. n = 6; *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: To evaluate the mechanism of knee loading effect on OA at the molecular level, we examined the activities of Wnt3a, together with NFATc1, RANKL, TNF-α, and Cathepsin K in the tibia. Immunohistochemistry staining of Wnt3a and NFATc1 further validated the effects of knee loading on promotion of Wnt3a and inhibition of NFATc1 in cartilage cells (Fig. 6A–D). Both western blot analysis and quantitative real-time PCR of proximal tibia showed that the expression of Wnt3a was significantly increased by knee loading. However, the protein and mRNA levels of NFATc1, RANKL, TNF-α, and Cathepsin K were significantly suppressed by knee loading (Fig. 6E,F and Supplementary Fig. S2).

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