The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice

A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the r...

Full description

Saved in:
Bibliographic Details
Published in:Calcified tissue international 2022-09, Vol.111 (3), p.313-322
Main Authors: Macica, Carolyn M., Luo, Jack, Tommasini, Steven M.
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Animal models
Biochemistry
Biomechanics
Biomedical and Life Sciences
Bone matrix
Cell Biology
Comorbidity
Endocrinology
Hyperplasia
Hypophosphatemia
Life Sciences
Mechanical loading
Mechanical properties
Mechanical unloading
Mineralization
Original Research
Orthopedics
Osteomalacia
Phosphatase
Sox9 protein
Unloading
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3
cites cdi_FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3
container_end_page 322
container_issue 3
container_start_page 313
container_title Calcified tissue international
container_volume 111
creator Macica, Carolyn M.
Luo, Jack
Tommasini, Steven M.
description A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the result of a hyperplastic expansion of resident alkaline phosphatase, Sox9-positive mineralizing fibrochondrocytes. Here, we hypothesized hyperplasia as a compensatory physical adaptation to aberrant mechanical stresses at the level of the entheses interface inserting into pathologically soft bone. To test this hypothesis, we examined the Achilles insertion of the triceps surae developed under normal and impaired loading conditions in Hyp and WT mice. Tensile stiffness, ultimate strength, and maximum strain were measured and compared. Biomechanical testing revealed that under normal loading conditions, despite inserting into a soft bone matrix, both the enthesophyte development (9 weeks) and progression (6–8 months) of Hyp mice were equivalent to the mechanical properties of WT mice. Unloading the insertion during development significantly reduced alkaline phosphatase, Sox9-positive fibrochondrocytes. In WT mice, this correlated with a decrease in stiffness and ultimate strength relative to the control limb, confirming the critical role of mechanical loading in the development of the enthesis. Most significantly, in response to unloading, maximum strain was increased in tensile tests only in the setting of subchondral osteomalacia of Hyp mice. These data suggest that mineralizing fibrochondrocyte expansion in XLH occurs as a compensatory adaptation to the soft bone matrix.
doi_str_mv 10.1007/s00223-022-00989-7
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2671264994</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2671264994</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3</originalsourceid><addsrcrecordid>eNp9kU1P3DAQhq0K1IWlf6CHyhKXXgLjj9hrbhQtLNIiLovUm-V1Jk1QEoc4W2n_fQ1LWcSBy9gzfuadkV9CvjM4YwD6PAJwLrIUMgAzM5n-Qo6YFCmdcX3w7j4hxzE-AjCplPpKJiJXbKa1OiLVqkI678YKY-jdWG1pKOnv5YLeRuroHfrKdbV3Db0sXD-6sQ4dHQO9jyOG1jXO1-6C_qpDuyfnf-sCO4-0HEJLF9ue3tUeT8hh6ZqI317PKXm4nq-uFtny_ub26nKZeaHzMZPAfK4LBzOpQGnDBaSSyEHmWhvGmDNCeS7Q4zoXUpYF6IIBauchN96LKfm50-2H8LTBONq2jh6bxnUYNtFypRlX0hiZ0NMP6GPYDF3aznINOTNGp9FTwneUH0KMA5a2H-rWDVvLwD77YHc-2BTsiw9Wp6Yfr9KbdYvFW8v_j0-A2AExPXV_cNjP_kT2HwgbkCk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2705199701</pqid></control><display><type>article</type><title>The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice</title><source>Springer Link</source><creator>Macica, Carolyn M. ; Luo, Jack ; Tommasini, Steven M.</creator><creatorcontrib>Macica, Carolyn M. ; Luo, Jack ; Tommasini, Steven M.</creatorcontrib><description>A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the result of a hyperplastic expansion of resident alkaline phosphatase, Sox9-positive mineralizing fibrochondrocytes. Here, we hypothesized hyperplasia as a compensatory physical adaptation to aberrant mechanical stresses at the level of the entheses interface inserting into pathologically soft bone. To test this hypothesis, we examined the Achilles insertion of the triceps surae developed under normal and impaired loading conditions in Hyp and WT mice. Tensile stiffness, ultimate strength, and maximum strain were measured and compared. Biomechanical testing revealed that under normal loading conditions, despite inserting into a soft bone matrix, both the enthesophyte development (9 weeks) and progression (6–8 months) of Hyp mice were equivalent to the mechanical properties of WT mice. Unloading the insertion during development significantly reduced alkaline phosphatase, Sox9-positive fibrochondrocytes. In WT mice, this correlated with a decrease in stiffness and ultimate strength relative to the control limb, confirming the critical role of mechanical loading in the development of the enthesis. Most significantly, in response to unloading, maximum strain was increased in tensile tests only in the setting of subchondral osteomalacia of Hyp mice. These data suggest that mineralizing fibrochondrocyte expansion in XLH occurs as a compensatory adaptation to the soft bone matrix.</description><identifier>ISSN: 1432-0827</identifier><identifier>ISSN: 0171-967X</identifier><identifier>EISSN: 1432-0827</identifier><identifier>DOI: 10.1007/s00223-022-00989-7</identifier><identifier>PMID: 35618776</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alkaline phosphatase ; Animal models ; Biochemistry ; Biomechanics ; Biomedical and Life Sciences ; Bone matrix ; Cell Biology ; Comorbidity ; Endocrinology ; Hyperplasia ; Hypophosphatemia ; Life Sciences ; Mechanical loading ; Mechanical properties ; Mechanical unloading ; Mineralization ; Original Research ; Orthopedics ; Osteomalacia ; Phosphatase ; Sox9 protein ; Unloading</subject><ispartof>Calcified tissue international, 2022-09, Vol.111 (3), p.313-322</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3</citedby><cites>FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3</cites><orcidid>0000-0002-1760-9678 ; 0000-0001-5118-5867</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35618776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Macica, Carolyn M.</creatorcontrib><creatorcontrib>Luo, Jack</creatorcontrib><creatorcontrib>Tommasini, Steven M.</creatorcontrib><title>The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice</title><title>Calcified tissue international</title><addtitle>Calcif Tissue Int</addtitle><addtitle>Calcif Tissue Int</addtitle><description>A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the result of a hyperplastic expansion of resident alkaline phosphatase, Sox9-positive mineralizing fibrochondrocytes. Here, we hypothesized hyperplasia as a compensatory physical adaptation to aberrant mechanical stresses at the level of the entheses interface inserting into pathologically soft bone. To test this hypothesis, we examined the Achilles insertion of the triceps surae developed under normal and impaired loading conditions in Hyp and WT mice. Tensile stiffness, ultimate strength, and maximum strain were measured and compared. Biomechanical testing revealed that under normal loading conditions, despite inserting into a soft bone matrix, both the enthesophyte development (9 weeks) and progression (6–8 months) of Hyp mice were equivalent to the mechanical properties of WT mice. Unloading the insertion during development significantly reduced alkaline phosphatase, Sox9-positive fibrochondrocytes. In WT mice, this correlated with a decrease in stiffness and ultimate strength relative to the control limb, confirming the critical role of mechanical loading in the development of the enthesis. Most significantly, in response to unloading, maximum strain was increased in tensile tests only in the setting of subchondral osteomalacia of Hyp mice. These data suggest that mineralizing fibrochondrocyte expansion in XLH occurs as a compensatory adaptation to the soft bone matrix.</description><subject>Alkaline phosphatase</subject><subject>Animal models</subject><subject>Biochemistry</subject><subject>Biomechanics</subject><subject>Biomedical and Life Sciences</subject><subject>Bone matrix</subject><subject>Cell Biology</subject><subject>Comorbidity</subject><subject>Endocrinology</subject><subject>Hyperplasia</subject><subject>Hypophosphatemia</subject><subject>Life Sciences</subject><subject>Mechanical loading</subject><subject>Mechanical properties</subject><subject>Mechanical unloading</subject><subject>Mineralization</subject><subject>Original Research</subject><subject>Orthopedics</subject><subject>Osteomalacia</subject><subject>Phosphatase</subject><subject>Sox9 protein</subject><subject>Unloading</subject><issn>1432-0827</issn><issn>0171-967X</issn><issn>1432-0827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU1P3DAQhq0K1IWlf6CHyhKXXgLjj9hrbhQtLNIiLovUm-V1Jk1QEoc4W2n_fQ1LWcSBy9gzfuadkV9CvjM4YwD6PAJwLrIUMgAzM5n-Qo6YFCmdcX3w7j4hxzE-AjCplPpKJiJXbKa1OiLVqkI678YKY-jdWG1pKOnv5YLeRuroHfrKdbV3Db0sXD-6sQ4dHQO9jyOG1jXO1-6C_qpDuyfnf-sCO4-0HEJLF9ue3tUeT8hh6ZqI317PKXm4nq-uFtny_ub26nKZeaHzMZPAfK4LBzOpQGnDBaSSyEHmWhvGmDNCeS7Q4zoXUpYF6IIBauchN96LKfm50-2H8LTBONq2jh6bxnUYNtFypRlX0hiZ0NMP6GPYDF3aznINOTNGp9FTwneUH0KMA5a2H-rWDVvLwD77YHc-2BTsiw9Wp6Yfr9KbdYvFW8v_j0-A2AExPXV_cNjP_kT2HwgbkCk</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Macica, Carolyn M.</creator><creator>Luo, Jack</creator><creator>Tommasini, Steven M.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1760-9678</orcidid><orcidid>https://orcid.org/0000-0001-5118-5867</orcidid></search><sort><creationdate>20220901</creationdate><title>The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice</title><author>Macica, Carolyn M. ; Luo, Jack ; Tommasini, Steven M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alkaline phosphatase</topic><topic>Animal models</topic><topic>Biochemistry</topic><topic>Biomechanics</topic><topic>Biomedical and Life Sciences</topic><topic>Bone matrix</topic><topic>Cell Biology</topic><topic>Comorbidity</topic><topic>Endocrinology</topic><topic>Hyperplasia</topic><topic>Hypophosphatemia</topic><topic>Life Sciences</topic><topic>Mechanical loading</topic><topic>Mechanical properties</topic><topic>Mechanical unloading</topic><topic>Mineralization</topic><topic>Original Research</topic><topic>Orthopedics</topic><topic>Osteomalacia</topic><topic>Phosphatase</topic><topic>Sox9 protein</topic><topic>Unloading</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Macica, Carolyn M.</creatorcontrib><creatorcontrib>Luo, Jack</creatorcontrib><creatorcontrib>Tommasini, Steven M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Proquest Nursing &amp; Allied Health Source</collection><collection>ProQuest_Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Calcified tissue international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Macica, Carolyn M.</au><au>Luo, Jack</au><au>Tommasini, Steven M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice</atitle><jtitle>Calcified tissue international</jtitle><stitle>Calcif Tissue Int</stitle><addtitle>Calcif Tissue Int</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>111</volume><issue>3</issue><spage>313</spage><epage>322</epage><pages>313-322</pages><issn>1432-0827</issn><issn>0171-967X</issn><eissn>1432-0827</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the result of a hyperplastic expansion of resident alkaline phosphatase, Sox9-positive mineralizing fibrochondrocytes. Here, we hypothesized hyperplasia as a compensatory physical adaptation to aberrant mechanical stresses at the level of the entheses interface inserting into pathologically soft bone. To test this hypothesis, we examined the Achilles insertion of the triceps surae developed under normal and impaired loading conditions in Hyp and WT mice. Tensile stiffness, ultimate strength, and maximum strain were measured and compared. Biomechanical testing revealed that under normal loading conditions, despite inserting into a soft bone matrix, both the enthesophyte development (9 weeks) and progression (6–8 months) of Hyp mice were equivalent to the mechanical properties of WT mice. Unloading the insertion during development significantly reduced alkaline phosphatase, Sox9-positive fibrochondrocytes. In WT mice, this correlated with a decrease in stiffness and ultimate strength relative to the control limb, confirming the critical role of mechanical loading in the development of the enthesis. Most significantly, in response to unloading, maximum strain was increased in tensile tests only in the setting of subchondral osteomalacia of Hyp mice. These data suggest that mineralizing fibrochondrocyte expansion in XLH occurs as a compensatory adaptation to the soft bone matrix.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35618776</pmid><doi>10.1007/s00223-022-00989-7</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1760-9678</orcidid><orcidid>https://orcid.org/0000-0001-5118-5867</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1432-0827
ispartof Calcified tissue international, 2022-09, Vol.111 (3), p.313-322
issn 1432-0827
0171-967X
1432-0827
language eng
recordid cdi_proquest_miscellaneous_2671264994
source Springer Link
subjects Alkaline phosphatase
Animal models
Biochemistry
Biomechanics
Biomedical and Life Sciences
Bone matrix
Cell Biology
Comorbidity
Endocrinology
Hyperplasia
Hypophosphatemia
Life Sciences
Mechanical loading
Mechanical properties
Mechanical unloading
Mineralization
Original Research
Orthopedics
Osteomalacia
Phosphatase
Sox9 protein
Unloading
title The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T06%3A38%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Enthesopathy%20of%20XLH%20Is%20a%20Mechanical%20Adaptation%20to%20Osteomalacia:%20Biomechanical%20Evidence%20from%20Hyp%20Mice&rft.jtitle=Calcified%20tissue%20international&rft.au=Macica,%20Carolyn%20M.&rft.date=2022-09-01&rft.volume=111&rft.issue=3&rft.spage=313&rft.epage=322&rft.pages=313-322&rft.issn=1432-0827&rft.eissn=1432-0827&rft_id=info:doi/10.1007/s00223-022-00989-7&rft_dat=%3Cproquest_cross%3E2671264994%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c375t-401c57da0846067923040135045779111a936c23eceb5344fd07d10e7ac059cc3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2705199701&rft_id=info:pmid/35618776&rfr_iscdi=true