The role of miR-150 regulates bone cell differentiation and function.
Histomorphometry; Micro-CT; miRNA-150; Osteoactivin/GPNMB; Osteoblast; Osteoclast
BACKGROUND: mir-RNAs play a role in regulating bone homeostasis. In this study we assessed the functional role of mir-RNA 150 in bone homeostasis. We also assess the effects of miR-150 deficiency on osteoblast and osteoclast differentiation and function using in vivo and in vitro approaches. METHODS: Wild type (WT) (C57BL/6J) and miR-150 KO mice were compared for a variety of parameters. Micro-CT imaging was conducted to quantify trabecular bone mass inferior to the distal growth plate of the femur. Von Kossa staining was performed for osteoblast culture mineralization.
Moussa FM; Cook Bryson P; Sondag GR; DeSanto M; Obri MS; McDermott SE; Safadi FF
Bone
2020
2020-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.bone.2020.115470" target="_blank" rel="noreferrer noopener">10.1016/j.bone.2020.115470</a>
A novel regulatory role of TRAPPC9 in L-plastin-mediated osteoclast actin ring formation
actin ring; cytoskeleton; L-plastin; osteoclast; protein trafficking; TRAPPC9; TRAPPII
Trafficking protein particle complex 9 (TRAPPC9) is a major subunit of the TRAPPII complex. TRAPPC9 has been reported to bind nuclear factor κB kinase subunit β (IKKβ) and NF-kB-inducing kinase (NIK) where it plays a role in the canonical and noncanonical of nuclear factor-κB (NF-kB) signaling pathways, receptively. The role of TRAPPC9 in protein trafficking and cytoskeleton organization in osteoclast (OC) has not been studied yet. In this study, we examined the mRNA expression of TRAPPC9 during OC differentiation. Next, we examined the colocalization of TRAPPC9 with cathepsin-K, known to mediate OC resorption suggesting that TRAPPC9 mediates the trafficking pathway within OC. To identify TRAPPC9 protein partners important for OC-mediated cytoskeleton re-organization, we conducted immunoprecipitation of TRAPPC9 in mature OCs followed by mass spectrometry analysis. Our data showed that TRAPPC9 binds various protein partners. One protein with high recovery rate is L-plastin (LPL). LPL localizes at the podosomes and reported to play a crucial role in actin aggregation thereby actin ring formation and OC function. Although the role of LPL in OC-mediated bone resorption has not fully reported in detail. Here, first, we confirmed the binding of LPL to TRAPPC9 and, then, we investigated the potential regulatory role of TRAPPC9 in LPL-mediated OC cytoskeleton reorganization. We assessed the localization of TRAPPC9 and LPL in OC and found that TRAPPC9 is colocalized with LPL at the periphery of OC. Next, we determined the effect of TRAPPC9 overexpression on LPL recruitment to the actin ring using a viral system. Interestingly, our data showed that TRAPPC9 overexpression promotes the recruitment of LPL to the actin ring when compared with control cultures. In addition, we observed that TRAPPC9 overexpression reorganizes actin clusters/aggregates and regulates vinculin recruitment into the OC periphery to initiate podosome formation.
Hussein Nazar J; Mbimba Thomas; Al-Adlaan Asaad A; Ansari Mohammad Y; Jaber Fatima A; McDermott Scott; Kasumov Takhar; Safadi Fayez F
Journal of Cellular Biochemistry
2019
2019-08
<a href="http://doi.org/10.1002/jcb.29168" target="_blank" rel="noreferrer noopener">10.1002/jcb.29168</a>
Autophagy plays an essential role in bone homeostasis.
osteoclast; autophagosome; autophagy; osteoblast; osteocytes
Autophagy is very critical for multiple cellular processes. Autophagy plays a critical role in bone cell differentiation and function.
Jaber Fatima A; Khan Nazir M; Ansari Mohammad Y; Al-Adlaan Asaad A; Hussein Nazar J; Safadi Fayez F
Journal of cellular physiology
2019
2019-02
<a href="http://doi.org/10.1002/jcp.27071" target="_blank" rel="noreferrer noopener">10.1002/jcp.27071</a>
Mutation in Osteoactivin Promotes Receptor Activator of NFkappaB Ligand (RANKL)-mediated Osteoclast Differentiation and Survival but Inhibits Osteoclast Function.
*Mutation; Akt; Animals; bone; bone marrow; Bone Remodeling; Cell Differentiation/*physiology; Cell Survival/*physiology; Eye Proteins/*genetics; Inbred DBA; MAP kinases (MAPKs); Membrane Glycoproteins/*genetics; Mice; osteoactivin; osteoclast; Osteoclasts/*cytology; osteopetrosis; RANK Ligand/metabolism/*physiology; Signal Transduction; X-Ray Microtomography
We previously reported on the importance of osteoactivin (OA/Gpnmb) in osteogenesis. In this study, we examined the role of OA in osteoclastogenesis, using mice with a nonsense mutation in the Gpnmb gene (D2J) and wild-type controls (D2J/Gpnmb(+)). In these D2J mice, micro-computed tomography and histomorphometric analyses revealed increased cortical thickness, whereas total porosity and eroded surface were significantly reduced in D2J mice compared with wild-type controls, and these results were corroborated by lower serum levels of
Abdelmagid Samir M; Sondag Gregory R; Moussa Fouad M; Belcher Joyce Y; Yu Bing; Stinnett Hilary; Novak Kimberly; Mbimba Thomas; Khol Matthew; Hankenson Kurt D; Malcuit Christopher; Safadi Fayez F
The Journal of biological chemistry
2015
2015-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1074/jbc.M114.624270" target="_blank" rel="noreferrer noopener">10.1074/jbc.M114.624270</a>