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CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

Li Y, Zhong G, Sun W, Zhao C, Zhang P, Song J, Zhao D, Jin X, Li Q, Ling S, Li Y - Sci Rep (2015)

Bottom Line: We found that CD44 expression was upregulated during osteoclastogenesis.CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice.These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.

ABSTRACT
The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

No MeSH data available.


Related in: MedlinePlus

Model of CD44-mediated pathway in osteoclast differentiation and activity.After RANKL stimulation, the CD44 expression in osteoclast cells was upregulated. CD44 could increase the interaction between RANK and TRAF6, then it would activate its downstream signaling molecules, lead the phosphorylation of Src or Akt, which phosphorylates IκB-α and promotes the expression of NFATc1. NFATc1 induces the expression of genes related to the function and activity of osteoclast.
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f6: Model of CD44-mediated pathway in osteoclast differentiation and activity.After RANKL stimulation, the CD44 expression in osteoclast cells was upregulated. CD44 could increase the interaction between RANK and TRAF6, then it would activate its downstream signaling molecules, lead the phosphorylation of Src or Akt, which phosphorylates IκB-α and promotes the expression of NFATc1. NFATc1 induces the expression of genes related to the function and activity of osteoclast.

Mentions: We demonstrated that the expression of CD44 is upregulated during M-CSF- and RANKL-induced osteoclastogenesis. CD44 KO resulted in a much lower expression of genes related to osteoclast differentiation and function in vitro. Osteoclasts induced from bone marrow-derived monocytes isolated from CD44 KO mice exhibited reduced activity and function by TRAP staining and bone resorption measurement. We also found that CD44 was involved in the regulation of osteoclastogenesis through NF-κB-mediated signaling pathway. CD44 enhanced the interaction between RANK and TRAF6 and faciliates its down-stream signaling. In the hindlimb unloading model, the expression of CD44 was significantly upregulated in the hindlimb bone. CD44 KO could protect from hindlimb unloading-induced cortical bone loss, whereby the downregulation of osteoclasts rather than osteoblasts contributed to this process. A model of the CD44-mediated pathway in osteoclast differentiation and activity is shown in Fig. 6.


CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

Li Y, Zhong G, Sun W, Zhao C, Zhang P, Song J, Zhao D, Jin X, Li Q, Ling S, Li Y - Sci Rep (2015)

Model of CD44-mediated pathway in osteoclast differentiation and activity.After RANKL stimulation, the CD44 expression in osteoclast cells was upregulated. CD44 could increase the interaction between RANK and TRAF6, then it would activate its downstream signaling molecules, lead the phosphorylation of Src or Akt, which phosphorylates IκB-α and promotes the expression of NFATc1. NFATc1 induces the expression of genes related to the function and activity of osteoclast.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4632082&req=5

f6: Model of CD44-mediated pathway in osteoclast differentiation and activity.After RANKL stimulation, the CD44 expression in osteoclast cells was upregulated. CD44 could increase the interaction between RANK and TRAF6, then it would activate its downstream signaling molecules, lead the phosphorylation of Src or Akt, which phosphorylates IκB-α and promotes the expression of NFATc1. NFATc1 induces the expression of genes related to the function and activity of osteoclast.
Mentions: We demonstrated that the expression of CD44 is upregulated during M-CSF- and RANKL-induced osteoclastogenesis. CD44 KO resulted in a much lower expression of genes related to osteoclast differentiation and function in vitro. Osteoclasts induced from bone marrow-derived monocytes isolated from CD44 KO mice exhibited reduced activity and function by TRAP staining and bone resorption measurement. We also found that CD44 was involved in the regulation of osteoclastogenesis through NF-κB-mediated signaling pathway. CD44 enhanced the interaction between RANK and TRAF6 and faciliates its down-stream signaling. In the hindlimb unloading model, the expression of CD44 was significantly upregulated in the hindlimb bone. CD44 KO could protect from hindlimb unloading-induced cortical bone loss, whereby the downregulation of osteoclasts rather than osteoblasts contributed to this process. A model of the CD44-mediated pathway in osteoclast differentiation and activity is shown in Fig. 6.

Bottom Line: We found that CD44 expression was upregulated during osteoclastogenesis.CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice.These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.

ABSTRACT
The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

No MeSH data available.


Related in: MedlinePlus