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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

Proposed mechanism of knee loading affects on OA by inhibiting osteoclast development.(A) A significant positive correlation was observed between osteoclast activity and cartilage degeneration. A significant negative correlation was observed between osteoclast activity and subchondral bone recovery. Subchondral bone recovery negatively correlated with cartilage degeneration. (B) Proposed molecular mechanism of knee loading suppresses osteoclastogenesis by Wnt signaling pathway.
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f7: Proposed mechanism of knee loading affects on OA by inhibiting osteoclast development.(A) A significant positive correlation was observed between osteoclast activity and cartilage degeneration. A significant negative correlation was observed between osteoclast activity and subchondral bone recovery. Subchondral bone recovery negatively correlated with cartilage degeneration. (B) Proposed molecular mechanism of knee loading suppresses osteoclastogenesis by Wnt signaling pathway.

Mentions: Furthermore, we also generated the multiple linear regression models to confirm osteoclast activity as a crucial factor for osteoarthritis. The mathematic models showed that increasing osteoclast formation and Oc.S/BS for osteoclast activity assessment, consistent with the increase in OARSI scores as evaluation of cartilage degeneration and decrease of SBP and B.Ar/T.Ar as structure changes of subchondral and trabecular bone. The multiple linear regression models showed osteoclast activity are significant predictors for the changes in OA, including prevented cartilage degradation and regulated subchondral bone remodeling. Osteoclasts originate from haemopoietic stem cells and activated osteoclasts are multinucleated giant cells for bone resorption involved as one of the two factors for bone remodeling3738. Inhibiting osteoclatic bone resorption has been reported in animal models of osteoarthritis treated with bisphosphonates such as alendronate and zolendronic acid394041. To verify the role of osteoclast activity in cartilage and subchondral bone, alendronate, which is an anti-osteoclastic bone resorption agent, was used as a positive control in OA. The results showed that knee loading as well as alendronate could decrease the OARSI scores and increase B.Ar/T.Ar, meanwhile, inhibit Oc.S/BS and osteoclast formation, migration, and adhesion. Therefore, the preventive effects of knee loading on cartilage and subchondral bone might be mainly explained by suppressing the osteoclast activity (Fig. 7A).


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)

Proposed mechanism of knee loading affects on OA by inhibiting osteoclast development.(A) A significant positive correlation was observed between osteoclast activity and cartilage degeneration. A significant negative correlation was observed between osteoclast activity and subchondral bone recovery. Subchondral bone recovery negatively correlated with cartilage degeneration. (B) Proposed molecular mechanism of knee loading suppresses osteoclastogenesis by Wnt signaling pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Proposed mechanism of knee loading affects on OA by inhibiting osteoclast development.(A) A significant positive correlation was observed between osteoclast activity and cartilage degeneration. A significant negative correlation was observed between osteoclast activity and subchondral bone recovery. Subchondral bone recovery negatively correlated with cartilage degeneration. (B) Proposed molecular mechanism of knee loading suppresses osteoclastogenesis by Wnt signaling pathway.
Mentions: Furthermore, we also generated the multiple linear regression models to confirm osteoclast activity as a crucial factor for osteoarthritis. The mathematic models showed that increasing osteoclast formation and Oc.S/BS for osteoclast activity assessment, consistent with the increase in OARSI scores as evaluation of cartilage degeneration and decrease of SBP and B.Ar/T.Ar as structure changes of subchondral and trabecular bone. The multiple linear regression models showed osteoclast activity are significant predictors for the changes in OA, including prevented cartilage degradation and regulated subchondral bone remodeling. Osteoclasts originate from haemopoietic stem cells and activated osteoclasts are multinucleated giant cells for bone resorption involved as one of the two factors for bone remodeling3738. Inhibiting osteoclatic bone resorption has been reported in animal models of osteoarthritis treated with bisphosphonates such as alendronate and zolendronic acid394041. To verify the role of osteoclast activity in cartilage and subchondral bone, alendronate, which is an anti-osteoclastic bone resorption agent, was used as a positive control in OA. The results showed that knee loading as well as alendronate could decrease the OARSI scores and increase B.Ar/T.Ar, meanwhile, inhibit Oc.S/BS and osteoclast formation, migration, and adhesion. Therefore, the preventive effects of knee loading on cartilage and subchondral bone might be mainly explained by suppressing the osteoclast activity (Fig. 7A).

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