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Article

CD44 Can Compensate for IgSF11 Deficiency by Associating with the Scaffold Protein PSD-95 during Osteoclast Differentiation

Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
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Int. J. Mol. Sci. 2020, 21(7), 2646; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072646
Received: 17 March 2020 / Revised: 8 April 2020 / Accepted: 9 April 2020 / Published: 10 April 2020
(This article belongs to the Special Issue Osteoclast Multinucleation Mechanisms)
Differentiation of osteoclasts, which are specialized multinucleated macrophages capable of bone resorption, is driven primarily by receptor activator of NF-κB ligand (RANKL). Additional signaling from cell surface receptors, such as cell adhesion molecules (CAMs), is also required for osteoclast maturation. Previously, we have demonstrated that immunoglobulin superfamily 11 (IgSF11), a member of the immunoglobulin-CAM (IgCAM) family, plays an important role in osteoclast differentiation through association with the scaffold protein postsynaptic density protein 95 (PSD-95). Here, we demonstrate that the osteoclast-expressed CAM CD44 can compensate for IgSF11 deficiency when cell–cell interaction conditions are suboptimal by associating with PSD-95. Impaired osteoclast differentiation in IgSF11-deficient (IgSF11−/−) cultures was rescued by antibody-mediated stimulation of CD44 or by treatment with low-molecular-weight hyaluronan (LMW-HA), a CD44 ligand. Biochemical analysis revealed that PSD-95, which is required for osteoclast differentiation, associates with CD44 in osteoclasts regardless of the presence or absence of IgSF11. RNAi-mediated knockdown of PSD-95 abrogated the effects of either CD44 stimulation or LMW-HA treatment on osteoclast differentiation, suggesting that CD44, similar to IgSF11, is functionally associated with PSD-95 during osteoclast differentiation. Taken together, these results reveal that CD44 can compensate for IgSF11 deficiency in osteoclasts through association with PSD-95. View Full-Text
Keywords: Osteoclast; CD44; IgSF11; PSD-95; differentiation Osteoclast; CD44; IgSF11; PSD-95; differentiation
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MDPI and ACS Style

Kim, H.; Takegahara, N.; Walsh, M.C.; Choi, Y. CD44 Can Compensate for IgSF11 Deficiency by Associating with the Scaffold Protein PSD-95 during Osteoclast Differentiation. Int. J. Mol. Sci. 2020, 21, 2646. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072646

AMA Style

Kim H, Takegahara N, Walsh MC, Choi Y. CD44 Can Compensate for IgSF11 Deficiency by Associating with the Scaffold Protein PSD-95 during Osteoclast Differentiation. International Journal of Molecular Sciences. 2020; 21(7):2646. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072646

Chicago/Turabian Style

Kim, Hyunsoo; Takegahara, Noriko; Walsh, Matthew C.; Choi, Yongwon. 2020. "CD44 Can Compensate for IgSF11 Deficiency by Associating with the Scaffold Protein PSD-95 during Osteoclast Differentiation" Int. J. Mol. Sci. 21, no. 7: 2646. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072646

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