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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 osteoclast activity in subchondral bone and bone marrow-derived cells.(A,B) TRAP staining of osteoclast in subchondral bone. Red color showed the TRAP-positive cells as osteoclasts in different magnification (A) 100 × (Bar = 200 μm), and (B) 400 × (Bar = 50 μm). Arrows indicated TRAP-positive cells. (C,D) Bone marrow-derived cells were seeded onto 96-well plates at a density of 1 × 105 cells/well. Cells were treated with M-CSF and RANKL for six days. TRAP-positive multinuclear cells (more than 3 nuclei) were identified as mature osteoclasts in different magnification (C) 100 × (Bar = 200 μm), and (D) 400 × (Bar = 50 μm). (E) Quantitative analysis of Oc.S/BS in the trabecular bone. (F) Quantitative analysis of the areas covered by TRAP-positive multinucleated osteoclasts. n = 10; ***P < 0.001.
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f3: Effects of knee loading on osteoclast activity in subchondral bone and bone marrow-derived cells.(A,B) TRAP staining of osteoclast in subchondral bone. Red color showed the TRAP-positive cells as osteoclasts in different magnification (A) 100 × (Bar = 200 μm), and (B) 400 × (Bar = 50 μm). Arrows indicated TRAP-positive cells. (C,D) Bone marrow-derived cells were seeded onto 96-well plates at a density of 1 × 105 cells/well. Cells were treated with M-CSF and RANKL for six days. TRAP-positive multinuclear cells (more than 3 nuclei) were identified as mature osteoclasts in different magnification (C) 100 × (Bar = 200 μm), and (D) 400 × (Bar = 50 μm). (E) Quantitative analysis of Oc.S/BS in the trabecular bone. (F) Quantitative analysis of the areas covered by TRAP-positive multinucleated osteoclasts. n = 10; ***P < 0.001.

Mentions: TRAP staining showed that osteoclasts in the subchondral bone were stained red in the surface of trabecular bone (black arrows), and OA mice showed the most TRAP positive cells among these 4 groups (Fig. 3A,B).


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 osteoclast activity in subchondral bone and bone marrow-derived cells.(A,B) TRAP staining of osteoclast in subchondral bone. Red color showed the TRAP-positive cells as osteoclasts in different magnification (A) 100 × (Bar = 200 μm), and (B) 400 × (Bar = 50 μm). Arrows indicated TRAP-positive cells. (C,D) Bone marrow-derived cells were seeded onto 96-well plates at a density of 1 × 105 cells/well. Cells were treated with M-CSF and RANKL for six days. TRAP-positive multinuclear cells (more than 3 nuclei) were identified as mature osteoclasts in different magnification (C) 100 × (Bar = 200 μm), and (D) 400 × (Bar = 50 μm). (E) Quantitative analysis of Oc.S/BS in the trabecular bone. (F) Quantitative analysis of the areas covered by TRAP-positive multinucleated osteoclasts. n = 10; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Effects of knee loading on osteoclast activity in subchondral bone and bone marrow-derived cells.(A,B) TRAP staining of osteoclast in subchondral bone. Red color showed the TRAP-positive cells as osteoclasts in different magnification (A) 100 × (Bar = 200 μm), and (B) 400 × (Bar = 50 μm). Arrows indicated TRAP-positive cells. (C,D) Bone marrow-derived cells were seeded onto 96-well plates at a density of 1 × 105 cells/well. Cells were treated with M-CSF and RANKL for six days. TRAP-positive multinuclear cells (more than 3 nuclei) were identified as mature osteoclasts in different magnification (C) 100 × (Bar = 200 μm), and (D) 400 × (Bar = 50 μm). (E) Quantitative analysis of Oc.S/BS in the trabecular bone. (F) Quantitative analysis of the areas covered by TRAP-positive multinucleated osteoclasts. n = 10; ***P < 0.001.
Mentions: TRAP staining showed that osteoclasts in the subchondral bone were stained red in the surface of trabecular bone (black arrows), and OA mice showed the most TRAP positive cells among these 4 groups (Fig. 3A,B).

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