FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption
There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitr...
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2025-01-01
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| author | Lei Wang Tarun Minocha Bhaba K. Das Mikaela D. Kunika Aarthi Kannan Ling Gao Subburaman Mohan Weirong Xing Kottayil I. Varughese Haibo Zhao |
| author_facet | Lei Wang Tarun Minocha Bhaba K. Das Mikaela D. Kunika Aarthi Kannan Ling Gao Subburaman Mohan Weirong Xing Kottayil I. Varughese Haibo Zhao |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro. In this study, we found that all three <i>Fam98</i> genes were expressed in precursor and mature osteoclasts. While the knockdown of Fam98c by a specific short-hairpin RNA (shRNA) in osteoclast precursors attenuated osteoclastogenesis, depletion of Fam98b by an shRNA specifically disrupted osteoclast lysosome trafficking and bone resorption with phenotypes similar to Fam98a shRNA-knockdown in our previous study. Loss of Fam98a in myeloid osteoclast precursors was dispensable for trabecular and cortical bone mass in mice, as well as osteoclastogenesis/bone resorption in vitro, possibly due to compensation by increased Fam98b expression in Fam98a-null osteoclasts. These findings indicate that the three Fam98 proteins play distinct roles in osteoclastogenesis and osteoclast function and need further investigation in future studies. |
| format | Article |
| id | doaj-art-4ef8a64375c14585a69110227b6dc5ea |
| institution | Kabale University |
| issn | 2079-7737 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-4ef8a64375c14585a69110227b6dc5ea2025-01-24T13:23:25ZengMDPI AGBiology2079-77372025-01-011414510.3390/biology14010045FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone ResorptionLei Wang0Tarun Minocha1Bhaba K. Das2Mikaela D. Kunika3Aarthi Kannan4Ling Gao5Subburaman Mohan6Weirong Xing7Kottayil I. Varughese8Haibo Zhao9Department of Orthopedics, The Third People’s Hospital of Hefei, Third Clinical College, Anhui Medical University, Hefei 230032, ChinaSouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USAMusculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAMusculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USASouthern California Institute for Research and Education, VA Long Beach Medical Center, Long Beach, CA 90822, USAThere are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro. In this study, we found that all three <i>Fam98</i> genes were expressed in precursor and mature osteoclasts. While the knockdown of Fam98c by a specific short-hairpin RNA (shRNA) in osteoclast precursors attenuated osteoclastogenesis, depletion of Fam98b by an shRNA specifically disrupted osteoclast lysosome trafficking and bone resorption with phenotypes similar to Fam98a shRNA-knockdown in our previous study. Loss of Fam98a in myeloid osteoclast precursors was dispensable for trabecular and cortical bone mass in mice, as well as osteoclastogenesis/bone resorption in vitro, possibly due to compensation by increased Fam98b expression in Fam98a-null osteoclasts. These findings indicate that the three Fam98 proteins play distinct roles in osteoclastogenesis and osteoclast function and need further investigation in future studies.https://www.mdpi.com/2079-7737/14/1/45Fam98aFam98bFam98costeoclastPlekhm1lysosome |
| spellingShingle | Lei Wang Tarun Minocha Bhaba K. Das Mikaela D. Kunika Aarthi Kannan Ling Gao Subburaman Mohan Weirong Xing Kottayil I. Varughese Haibo Zhao FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption Biology Fam98a Fam98b Fam98c osteoclast Plekhm1 lysosome |
| title | FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption |
| title_full | FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption |
| title_fullStr | FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption |
| title_full_unstemmed | FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption |
| title_short | FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption |
| title_sort | fam98 family proteins play distinct roles in osteoclastogenesis and bone resorption |
| topic | Fam98a Fam98b Fam98c osteoclast Plekhm1 lysosome |
| url | https://www.mdpi.com/2079-7737/14/1/45 |
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