Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium‐Dependent 1A
Objective Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclea...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2020-05, Vol.72 (5), p.750-760 |
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| creator | Kwon, Oh Chan Choi, Bongkun Lee, Eun‐Jin Park, Ji‐Eun Lee, Eun‐Ju Kim, Eun‐Young Kim, Sang‐Min Shin, Min‐Kyung Kim, Tae‐Hwan Hong, Seokchan Lee, Chang‐Keun Yoo, Bin Robinson, William H. Kim, Yong‐Gil Chang, Eun‐Ju |
| description | Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA. |
| doi_str_mv | 10.1002/art.41180 |
| format | Article |
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Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.]]></description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.41180</identifier><identifier>PMID: 31762216</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acid phosphatase ; Acid phosphatase (tartrate-resistant) ; Acid resistance ; Activation ; Adult ; Animals ; Ankylosing spondylitis ; Ankylosis ; Arthritis ; Axial skeleton ; Biomedical materials ; Bone growth ; Bone marrow ; Bone mass ; Bone turnover ; Cell Differentiation ; Computed tomography ; Correlation analysis ; Differentiation ; Evaluation ; Female ; Flow cytometry ; Fluorescence ; Gene expression ; Humans ; Inflammation ; Inflammatory diseases ; Leukocytes (mononuclear) ; Macrophages ; Magnesium ; Male ; Metabolism ; Mice ; Mice, Knockout ; mRNA ; Osteoblastogenesis ; Osteoclastogenesis ; Osteoclasts - physiology ; Osteogenesis ; Osteoprogenitor cells ; Phenotypes ; Phosphatase ; Polymerase chain reaction ; Precursors ; Protein Phosphatase 2C - physiology ; Proteins ; RANK Ligand - physiology ; Toll-like receptors ; Western blotting</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2020-05, Vol.72 (5), p.750-760</ispartof><rights>2019, American College of Rheumatology</rights><rights>2019, American College of Rheumatology.</rights><rights>2020, American College of Rheumatology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3530-10e4686fe317dced5f64d171cc30b28597d5f18de51c039900de2e61e4c3394a3</citedby><cites>FETCH-LOGICAL-c3530-10e4686fe317dced5f64d171cc30b28597d5f18de51c039900de2e61e4c3394a3</cites><orcidid>0000-0002-8029-7355 ; 0000-0002-3542-2276</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.41180$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.41180$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31762216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwon, Oh Chan</creatorcontrib><creatorcontrib>Choi, Bongkun</creatorcontrib><creatorcontrib>Lee, Eun‐Jin</creatorcontrib><creatorcontrib>Park, Ji‐Eun</creatorcontrib><creatorcontrib>Lee, Eun‐Ju</creatorcontrib><creatorcontrib>Kim, Eun‐Young</creatorcontrib><creatorcontrib>Kim, Sang‐Min</creatorcontrib><creatorcontrib>Shin, Min‐Kyung</creatorcontrib><creatorcontrib>Kim, Tae‐Hwan</creatorcontrib><creatorcontrib>Hong, Seokchan</creatorcontrib><creatorcontrib>Lee, Chang‐Keun</creatorcontrib><creatorcontrib>Yoo, Bin</creatorcontrib><creatorcontrib>Robinson, William H.</creatorcontrib><creatorcontrib>Kim, Yong‐Gil</creatorcontrib><creatorcontrib>Chang, Eun‐Ju</creatorcontrib><title>Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium‐Dependent 1A</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description><![CDATA[Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.]]></description><subject>Acid phosphatase</subject><subject>Acid phosphatase (tartrate-resistant)</subject><subject>Acid resistance</subject><subject>Activation</subject><subject>Adult</subject><subject>Animals</subject><subject>Ankylosing spondylitis</subject><subject>Ankylosis</subject><subject>Arthritis</subject><subject>Axial skeleton</subject><subject>Biomedical materials</subject><subject>Bone growth</subject><subject>Bone marrow</subject><subject>Bone mass</subject><subject>Bone turnover</subject><subject>Cell Differentiation</subject><subject>Computed tomography</subject><subject>Correlation analysis</subject><subject>Differentiation</subject><subject>Evaluation</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Fluorescence</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>Leukocytes (mononuclear)</subject><subject>Macrophages</subject><subject>Magnesium</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>mRNA</subject><subject>Osteoblastogenesis</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts - physiology</subject><subject>Osteogenesis</subject><subject>Osteoprogenitor cells</subject><subject>Phenotypes</subject><subject>Phosphatase</subject><subject>Polymerase chain reaction</subject><subject>Precursors</subject><subject>Protein Phosphatase 2C - physiology</subject><subject>Proteins</subject><subject>RANK Ligand - physiology</subject><subject>Toll-like receptors</subject><subject>Western blotting</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKAzEUhoMoKurCF5CAG11UT5KZdLIs9Qpeiuh6SDNn6pSZSU0ySnc-gs_ok5ja6kIwmxzCl4-f8xOyz-CEAfBT7cJJwlgGa2SbCy57KYd0_Wdmim2RPe-nEI_qg4R0k2wJ1pecM7lNpnc40aF6RfqAk66Oo22pLem9D2hNrX2gQ9s0VWiwDXQ8p9dtcNpgXUfY0ZGzAauWjp6tnz3roD3SWz1p0Vdd8_n-cYYzbIvFVzbYJRulrj3ure4d8nRx_ji86t3cX14PBzc9I1IBPQaYyEyWGEMWBou0lEnB-swYAWOepaofn1hWYMoMCKUACuQoGSZGCJVosUOOlt6Zsy8d-pA3lV8k1i3azuc8ipUEDllED_-gU9u5NqaLlEriklQqInW8pIyz3jss85mrGu3mOYN80UEeO8i_O4jswcrYjRssfsmfjUfgdAm8VTXO_zflg4fHpfILudeQ3Q</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Kwon, Oh Chan</creator><creator>Choi, Bongkun</creator><creator>Lee, Eun‐Jin</creator><creator>Park, Ji‐Eun</creator><creator>Lee, Eun‐Ju</creator><creator>Kim, Eun‐Young</creator><creator>Kim, Sang‐Min</creator><creator>Shin, Min‐Kyung</creator><creator>Kim, Tae‐Hwan</creator><creator>Hong, Seokchan</creator><creator>Lee, Chang‐Keun</creator><creator>Yoo, Bin</creator><creator>Robinson, William H.</creator><creator>Kim, Yong‐Gil</creator><creator>Chang, Eun‐Ju</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8029-7355</orcidid><orcidid>https://orcid.org/0000-0002-3542-2276</orcidid></search><sort><creationdate>202005</creationdate><title>Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium‐Dependent 1A</title><author>Kwon, Oh Chan ; Choi, Bongkun ; Lee, Eun‐Jin ; Park, Ji‐Eun ; Lee, Eun‐Ju ; Kim, Eun‐Young ; Kim, Sang‐Min ; Shin, Min‐Kyung ; Kim, Tae‐Hwan ; Hong, Seokchan ; Lee, Chang‐Keun ; Yoo, Bin ; Robinson, William H. ; Kim, Yong‐Gil ; Chang, Eun‐Ju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3530-10e4686fe317dced5f64d171cc30b28597d5f18de51c039900de2e61e4c3394a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acid phosphatase</topic><topic>Acid phosphatase (tartrate-resistant)</topic><topic>Acid resistance</topic><topic>Activation</topic><topic>Adult</topic><topic>Animals</topic><topic>Ankylosing spondylitis</topic><topic>Ankylosis</topic><topic>Arthritis</topic><topic>Axial skeleton</topic><topic>Biomedical materials</topic><topic>Bone growth</topic><topic>Bone marrow</topic><topic>Bone mass</topic><topic>Bone turnover</topic><topic>Cell Differentiation</topic><topic>Computed tomography</topic><topic>Correlation analysis</topic><topic>Differentiation</topic><topic>Evaluation</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Fluorescence</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>Leukocytes (mononuclear)</topic><topic>Macrophages</topic><topic>Magnesium</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>mRNA</topic><topic>Osteoblastogenesis</topic><topic>Osteoclastogenesis</topic><topic>Osteoclasts - physiology</topic><topic>Osteogenesis</topic><topic>Osteoprogenitor cells</topic><topic>Phenotypes</topic><topic>Phosphatase</topic><topic>Polymerase chain reaction</topic><topic>Precursors</topic><topic>Protein Phosphatase 2C - physiology</topic><topic>Proteins</topic><topic>RANK Ligand - physiology</topic><topic>Toll-like receptors</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwon, Oh Chan</creatorcontrib><creatorcontrib>Choi, Bongkun</creatorcontrib><creatorcontrib>Lee, Eun‐Jin</creatorcontrib><creatorcontrib>Park, Ji‐Eun</creatorcontrib><creatorcontrib>Lee, Eun‐Ju</creatorcontrib><creatorcontrib>Kim, Eun‐Young</creatorcontrib><creatorcontrib>Kim, Sang‐Min</creatorcontrib><creatorcontrib>Shin, Min‐Kyung</creatorcontrib><creatorcontrib>Kim, Tae‐Hwan</creatorcontrib><creatorcontrib>Hong, Seokchan</creatorcontrib><creatorcontrib>Lee, Chang‐Keun</creatorcontrib><creatorcontrib>Yoo, Bin</creatorcontrib><creatorcontrib>Robinson, William H.</creatorcontrib><creatorcontrib>Kim, Yong‐Gil</creatorcontrib><creatorcontrib>Chang, Eun‐Ju</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwon, Oh Chan</au><au>Choi, Bongkun</au><au>Lee, Eun‐Jin</au><au>Park, Ji‐Eun</au><au>Lee, Eun‐Ju</au><au>Kim, Eun‐Young</au><au>Kim, Sang‐Min</au><au>Shin, Min‐Kyung</au><au>Kim, Tae‐Hwan</au><au>Hong, Seokchan</au><au>Lee, Chang‐Keun</au><au>Yoo, Bin</au><au>Robinson, William H.</au><au>Kim, Yong‐Gil</au><au>Chang, Eun‐Ju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium‐Dependent 1A</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2020-05</date><risdate>2020</risdate><volume>72</volume><issue>5</issue><spage>750</spage><epage>760</epage><pages>750-760</pages><issn>2326-5191</issn><eissn>2326-5205</eissn><abstract><![CDATA[Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.]]></abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31762216</pmid><doi>10.1002/art.41180</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8029-7355</orcidid><orcidid>https://orcid.org/0000-0002-3542-2276</orcidid></addata></record> |
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| ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2020-05, Vol.72 (5), p.750-760 |
| issn | 2326-5191 2326-5205 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Acid phosphatase Acid phosphatase (tartrate-resistant) Acid resistance Activation Adult Animals Ankylosing spondylitis Ankylosis Arthritis Axial skeleton Biomedical materials Bone growth Bone marrow Bone mass Bone turnover Cell Differentiation Computed tomography Correlation analysis Differentiation Evaluation Female Flow cytometry Fluorescence Gene expression Humans Inflammation Inflammatory diseases Leukocytes (mononuclear) Macrophages Magnesium Male Metabolism Mice Mice, Knockout mRNA Osteoblastogenesis Osteoclastogenesis Osteoclasts - physiology Osteogenesis Osteoprogenitor cells Phenotypes Phosphatase Polymerase chain reaction Precursors Protein Phosphatase 2C - physiology Proteins RANK Ligand - physiology Toll-like receptors Western blotting |
| title | Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium‐Dependent 1A |
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