Knockdown of CD44 inhibits the alteration of osteoclast function induced by simulated microgravity

Abstract

Mechanical forces are essential to maintain skeletal homeostasis, and microgravity exposure leads to bone loss. During space flight, bone mineral density is decreased because of the inactivation of osteoblast and activation of osteoclast. However, the underlying molecular mechanism is still not clear. CD44 acts as a cellular surface adhesion molecule, which plays an important role in signal transduction between cells. Numerous studies have shown that CD44 plays diverse roles in promoting pre-osteoclast fusion. However, the role of CD44 in the alteration of osteoclast function induced by simulated microgravity remains to be fully elucidated. In this work, we utilized a ground-based, microgravity-simulation system, the Rotating Wall Vessel Bioreactor (RWVB). Using the RWVB, we demonstrated that simulated microgravity enhanced osteoclast function, meantime CD44 mRNA and protein levels were significantly increased. To verify the effects of CD44 on alteration of osteoclast function induced by simulated microgravity, specific siRNAs targeting CD44 were transfected. The results showed knockdown of CD44 inhibited the alteration of osteoclast function induced by simulated microgravity. Moreover, we found that clinorotation activated the NF-κB/NFATc1-mediated signaling pathway, which was downregulated after knockdown of CD44. Our study provided evidence that CD44 positively regulated osteoclast function and therapeutic suppression of CD44 may counteract bone loss induced by simulated microgravity.