{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:47:26Z","timestamp":1790221646834,"version":"4.1.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>Periostin and osteopontin are matricellular proteins abundantly expressed in bone fracture callus. Null mutation of either the periostin (<jats:italic>Postn<\/jats:italic>) gene or the osteopontin (<jats:italic>Spp1<\/jats:italic>) gene can impair bone fracture healing. However, the cell and molecular pathways affected by loss of POSTN or SPP1 which lead to impaired fracture healing are not well understood. To identify potential pathways, a detailed radiological, histological, and immunohistochemical analysis of femur fracture healing in <jats:italic>Postn<\/jats:italic>-null (<jats:italic>Postn<\/jats:italic>KO), <jats:italic>Spp1<\/jats:italic>-null (<jats:italic>Spp1<\/jats:italic>KO), and normal (WT) mice was performed. Apparent changes in specific protein levels identified by immunohistochemistry were confirmed by mRNA quantitation. Comparisons between the <jats:italic>Postn<\/jats:italic>KO and <jats:italic>Spp1<\/jats:italic>KO fracture calluses were confounded by interactions between the two genes; loss of <jats:italic>Postn<\/jats:italic> reduced <jats:italic>Spp1<\/jats:italic> expression and loss of <jats:italic>Spp1<\/jats:italic> reduced <jats:italic>Postn<\/jats:italic> expression. Consequently, alterations in fracture healing between mice heterozygous for the <jats:italic>Postn<\/jats:italic>-null allele (<jats:italic>Postn<\/jats:italic>HET) as well as the <jats:italic>Postn<\/jats:italic>KO and <jats:italic>Spp1<\/jats:italic>KO mice were similar. Calluses from <jats:italic>Postn<\/jats:italic>HET, <jats:italic>Postn<\/jats:italic>KO, and <jats:italic>Spp1<\/jats:italic>KO mice all had dysmorphic chondro-osseous junctions and reduced numbers of osteoclasts. The dysmorphic chondro-osseous junctions in the <jats:italic>Postn<\/jats:italic>HET, <jats:italic>Postn<\/jats:italic>KO, and <jats:italic>Spp1<\/jats:italic>KO calluses were associated with reduced numbers of MMP-13 expressing hypertrophic chondrocytes, consistent with delayed cartilage resolution. Unlike collagen X expressing callus chondrocytes, chondrocytes only expressed MMP-13 when localized to the chondro-osseous junction or after traversing the chondro-osseous junction. Cyclooxygenase-2 (COX-2) expression also appeared to be reduced in osteoclasts from the <jats:italic>Postn<\/jats:italic>HET, <jats:italic>Postn<\/jats:italic>KO, and <jats:italic>Spp1<\/jats:italic>KO calluses, including in those osteoclasts localized at the chondro-osseous junction. The results indicate that POSTN and SPP1 are necessary for normal chondro-osseous junction formation and that signaling from the chondro-osseous junction, possibly from COX-2 expressing osteoclasts, regulates callus vasculogenesis and chondrocyte hypertrophy necessary for endochondral ossification during fracture healing.<\/jats:p>","DOI":"10.3389\/ebm.2024.10066","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T04:11:34Z","timestamp":1737519094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Impaired fracture healing is associated with callus chondro-osseous junction abnormalities in periostin-null and osteopontin-null mice"],"prefix":"10.3389","volume":"249","author":[{"given":"Marc","family":"Teitelbaum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya D.","family":"Culbertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Wetterstrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Patrick","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"B1","first-page":"31","article-title":"Biology of fracture repair","volume-title":"Skeletal Trauma","author":"Schenk","year":"1992"},{"key":"B2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2106\/00004623-197254020-00010","article-title":"Oxygen tension of healing fractures in the rabbit","volume":"54","author":"Brighton","year":"1972","journal-title":"The J Bone and Joint Surg"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1911","DOI":"10.1002\/term.2622","article-title":"The roles of cellular and molecular components of a hematoma at early stage of bone healing","volume":"12","author":"Shiu","year":"2018","journal-title":"J Tissue Eng Regen Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2886","DOI":"10.2106\/jbjs.h.01878","article-title":"Effect of selective sensory denervation on fracture-healing: an experimental study of rats","volume":"91","author":"Apel","year":"2009","journal-title":"The J Bone Joint Surgery-American Volume"},{"key":"B5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s11914-017-0381-0","article-title":"Osteoimmunology in bone fracture healing","volume":"15","author":"Ono","year":"2017","journal-title":"Curr Osteoporos Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1002\/jor.23440","article-title":"Osteoclast depletion with clodronate liposomes delays fracture healing in mice","volume":"35","author":"Lin","year":"2017","journal-title":"J Orthop Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2220\/biomedres.34.119","article-title":"Histochemical aspects of the vascular invasion at the erosion zone of the epiphyseal cartilage in MMP-9-deficient mice","volume":"34","author":"Kojima","year":"2013","journal-title":"Biomed Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1242\/dev.130807","article-title":"Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes","volume":"144","author":"Hu","year":"2017","journal-title":"Development"},{"key":"B9","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/9467","article-title":"VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation","volume":"5","author":"Gerber","year":"1999","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/s8756-3282(01)00608-1","article-title":"Prevention of fracture healing in rats by an inhibitor of angiogenesis","volume":"29","author":"Hausman","year":"2001","journal-title":"Bone"},{"key":"B11","doi-asserted-by":"publisher","first-page":"161","DOI":"10.3109\/03008207.2016.1140752","article-title":"The cast of clasts: catabolism and vascular invasion during bone growth, repair, and disease by osteoclasts, chondroclasts, and septoclasts","volume":"57","author":"Odgren","year":"2016","journal-title":"Connect Tissue Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1002\/jor.23213","article-title":"Variation in lipid mediator and cytokine levels during mouse femur fracture healing","volume":"34","author":"Lin","year":"2016","journal-title":"J Orthop Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/jor.24170","article-title":"Cellular biology of fracture healing","volume":"37","author":"Bahney","year":"2019","journal-title":"J Orthopaedic Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.3390\/ijms24043569","article-title":"Landscape of well- coordinated fracture healing in a mouse model using molecular and cellular analysis","volume":"24","author":"Malhan","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/s0955-0674(02)00361-7","article-title":"Matricellular proteins: extracellular modulators of cell function","volume":"14","author":"Bornstein","year":"2002","journal-title":"Curr Opin Cell Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.mce.2015.12.014","article-title":"Periostin action in bone","volume":"432","author":"Bonnet","year":"2016","journal-title":"Mol Cell Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1002\/jbmr.5650091007","article-title":"Localization of the mRNA for bone matrix proteins during fracture healing as determined by in situ hybridization","volume":"9","author":"Hirakawa","year":"1994","journal-title":"J Bone Mineral Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.orthres.2003.10.007","article-title":"Gene expression of periostin in the early stage of fracture healing detected by cDNA microarray analysis","volume":"22","author":"Nakazawa","year":"2004","journal-title":"J Orthopaedic Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1359\/jbmr.061103","article-title":"Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice","volume":"22","author":"Duvall","year":"2007","journal-title":"J Bone Mineral Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41467-018-03124-z","article-title":"Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin","volume":"9","author":"Duchamp de Lageneste","year":"2018","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"11131","DOI":"10.1128\/mcb.25.24.11131-11144.2005","article-title":"Periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype","volume":"25","author":"Rios","year":"2005","journal-title":"Mol Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1172\/jci2131","article-title":"Altered wound healing in mice lacking a functional osteopontin gene (spp1)","volume":"101","author":"Liaw","year":"1998","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.clinbiochem.2018.07.003","article-title":"The multiple functions and mechanisms of osteopontin","volume":"59","author":"Icer","year":"2018","journal-title":"Clin Biochem"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4473","DOI":"10.1073\/pnas.87.12.4473","article-title":"Osteopontin--a possible anchor of osteoclasts to bone","volume":"87","author":"Reinholt","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1084\/jem.193.3.399","article-title":"Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin","volume":"193","author":"Ishijima","year":"2001","journal-title":"The J Exp Med Exp Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-981-13-6657-4_6","article-title":"Periostin in bone regeneration","volume":"1132","author":"Duchamp de Lageneste","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1002\/jor.25439","article-title":"Age-related decrease in periostin expression may be associated with attenuated fracture healing in old mice","volume":"41","author":"Clark","year":"2023","journal-title":"J Orthopaedic Res Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00774-023-01409-y","article-title":"Periostin splice variants affect craniofacial growth by influencing chondrocyte hypertrophy","volume":"41","author":"Ishihara","year":"2023","journal-title":"J Bone Miner Metab"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1007\/s00198-011-1892-7","article-title":"The multiple facets of periostin in bone metabolism","volume":"23","author":"Merle","year":"2012","journal-title":"Osteoporos Int Int"},{"key":"B30","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0065-1281(98)80015-9","article-title":"Switch of osteonectin and osteopontin mRNA expression in the process of cartilage-to-bone transition during fracture repair","volume":"100","author":"Nakase","year":"1998","journal-title":"Acta Histochem"},{"key":"B31","doi-asserted-by":"publisher","first-page":"20369","DOI":"10.1016\/s0021-9258(18)54932-2","article-title":"Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts","volume":"266","author":"Miyauchi","year":"1991","journal-title":"J Biol Chem"},{"key":"B32","first-page":"5358","article-title":"Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility","volume":"62","author":"Gillan","year":"2002","journal-title":"Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e88423","DOI":"10.1371\/journal.pone.0088423","article-title":"Immunohistochemical localization of key arachidonic acid metabolism enzymes during fracture healing in mice","volume":"9","author":"Lin","year":"2014","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"16737","DOI":"10.1016\/s0021-9258(19)85479-0","article-title":"Biochemical characterization of human osteoclast integrins. Osteoclasts express alpha v beta 3, alpha 2 beta 1, and alpha v beta 1 integrins","volume":"268","author":"Nesbitt","year":"1993","journal-title":"J Biol Chem"},{"key":"B35","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1161\/circresaha.107.149047","article-title":"Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling","volume":"101","author":"Oka","year":"2007","journal-title":"Circ Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/jcb.21224","article-title":"Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues","volume":"101","author":"Norris","year":"2007","journal-title":"J Cell Biochem"},{"key":"B37","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1097\/00005131-200411000-00006","article-title":"Characterization of a closed femur fracture model in mice","volume":"18","author":"Manigrasso","year":"2004","journal-title":"J Orthop Trauma"},{"key":"B38","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ab.2014.10.004","article-title":"Method for measuring lipid mediators, proteins, and messenger RNAs from a single tissue specimen","volume":"469","author":"Cottrell","year":"2015","journal-title":"Anal Biochem"},{"key":"B39","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/s0165-022x(00)00129-9","article-title":"Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR","volume":"46","author":"Schmittgen","year":"2000","journal-title":"J Biochem Biophysical Methods"},{"key":"B40","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.diff.2023.09.005","article-title":"Type H vessels in osteogenesis, homeostasis, and related disorders","volume":"134","author":"Qin","year":"2023","journal-title":"Differentiation"},{"key":"B41","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/978-3-319-61115-0_20","article-title":"The role of sex steroids in angiogenesis","volume-title":"Biochemical basis and therapeutic implications of angiogenesis","author":"Lam","year":"2017"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.1210\/en.2008-0355","article-title":"Sex dimorphism in wound healing: the roles of sex steroids and macrophage migration inhibitory factor","volume":"149","author":"Gilliver","year":"2008","journal-title":"Endocrinology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/s00335-002-2222-3","article-title":"Sexually dimorphic genes regulate healing and regeneration in MRL mice","volume":"14","author":"Blankenhorn","year":"2003","journal-title":"Mamm Genome"},{"key":"B44","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1002\/(sici)1097-4644(20000615)77:4<678::aid-jcb15>3.0.co;2-p","article-title":"MMP-13 is induced during chondrocyte hypertrophy","volume":"77","author":"D'Angelo","year":"2000","journal-title":"J Cell Biochem"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.joca.2021.06.001","article-title":"Inhibition of sphingosine 1phosphate protects mice against chondrocyte catabolism and osteoarthritis","volume":"29","author":"Cherifi","year":"2021","journal-title":"Osteoarthritis and Cartilage Cartilage"},{"key":"B46","doi-asserted-by":"publisher","first-page":"22708","DOI":"10.1038\/s41598-021-02246-7","article-title":"Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints initiates osteoclastmediated cartilage degradation by MMPs","volume":"11","author":"Larrouture","year":"2021","journal-title":"Sci Rep"},{"key":"B47","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.bbrc.2004.11.074","article-title":"Differential regulation of EP receptor isoforms during chondrogenesis and chondrocyte maturation","volume":"328","author":"Clark","year":"2005","journal-title":"Biochem Biophysical Res Commun"},{"key":"B48","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1136\/ard.2009.118620","article-title":"Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes","volume":"70","author":"Sato","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"B49","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.4049\/jimmunol.181.7.5082","article-title":"Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor","volume":"181","author":"Attur","year":"2008","journal-title":"The J Immunol"},{"key":"B50","first-page":"187","article-title":"Correlation of COX-2 and MMP-13 expressions with gastric cancer and their effects on prognosis","volume":"24","author":"Ren","year":"2019","journal-title":"J Buon"},{"key":"B51","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/jor.22770","article-title":"PPAR\u03b3 is involved in the hyperglycemia-induced inflammatory responses and collagen degradation in human chondrocytes and diabetic mouse cartilages","volume":"33","author":"Chen","year":"2015","journal-title":"J Orthopaedic Res"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1172\/jci80276","article-title":"Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease","volume":"126","author":"Fu","year":"2016","journal-title":"J Clin Invest"},{"key":"B53","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s8756-3282(99)00157-x","article-title":"Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice","volume":"25","author":"Yamagiwa","year":"1999","journal-title":"Bone"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e1150","DOI":"10.1371\/journal.pone.0001150","article-title":"Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration","volume":"2","author":"Behonick","year":"2007","journal-title":"PLoS ONE"},{"key":"B55","doi-asserted-by":"publisher","first-page":"5883","DOI":"10.1242\/dev.01461","article-title":"Altered endochondral bone development in matrix metalloproteinase 13-deficient mice","volume":"131","author":"Stickens","year":"2004","journal-title":"Development"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1007\/s00296-012-2548-4","article-title":"Phosphorylation of osteopontin in osteoarthritis degenerative cartilage and its effect on matrix metalloprotease 13","volume":"33","author":"Xu","year":"2013","journal-title":"Rheumatol Int"},{"key":"B57","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13075-021-02477-z","article-title":"Periostin loss-of-function protects mice from post-traumatic and agerelated osteoarthritis","volume":"23","author":"Attur","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B58","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.bbrc.2006.12.234","article-title":"Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice","volume":"354","author":"Kosaki","year":"2007","journal-title":"Biochem Biophysical Res Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/s0092-8674(00)81433-6","article-title":"Cyclooxygenase regulates angiogenesis induced by colon cancer cells","volume":"93","author":"Tsujii","year":"1998","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/s1479-666x(09)80042-5","article-title":"COX-2, VEGF and tumour angiogenesis","volume":"7","author":"Toomey","year":"2009","journal-title":"The Surgeon"},{"key":"B61","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3181\/00379727-172-41548","article-title":"PGE2 and angiogenesis","volume":"172","author":"Form","year":"1983","journal-title":"Exp Biol Med Exp Biol Med Soc Exp Biol Med"},{"key":"B62","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1146\/annurev.pharmtox.38.1.97","article-title":"Cyclooxygenases 1 and 2","volume":"38","author":"Vane","year":"1998","journal-title":"Annu Rev Pharmacol Toxicol Toxicol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"19819","DOI":"10.1074\/jbc.m002079200","article-title":"Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-knockout mice","volume":"275","author":"Miyaura","year":"2000","journal-title":"J Biol Chem"},{"key":"B64","doi-asserted-by":"publisher","first-page":"4","DOI":"10.21037\/sci-2022-038","article-title":"The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives","volume":"10","author":"Frade","year":"2023","journal-title":"Stem Cell Investig"},{"key":"B65","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.bone.2005.11.017","article-title":"Matricellular proteins: extracellular modulators of bone development, remodeling, and regeneration","volume":"38","author":"Alford","year":"2006","journal-title":"Bone"},{"key":"B66","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1002\/jbmr.2409","article-title":"ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation","volume":"30","author":"Chen","year":"2015","journal-title":"J Bone Mineral Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/bs.ctdb.2018.11.003","article-title":"ECM signaling in cartilage development and endochondral ossification","volume":"133","author":"Prein","year":"2019","journal-title":"Curr Top Dev Biol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1002\/jor.20544","article-title":"Altered osteoclast development and function in osteopontin deficient mice","volume":"26","author":"Franzen","year":"2008","journal-title":"J Orthopaedic Res"},{"key":"B69","doi-asserted-by":"publisher","first-page":"9901","DOI":"10.1016\/s0021-9258(18)98430-9","article-title":"Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption","volume":"268","author":"Ross","year":"1993","journal-title":"J Biol Chem"},{"key":"B70","doi-asserted-by":"publisher","first-page":"4107","DOI":"10.1096\/fj.15-272427","article-title":"Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation via matrix metalloproteinase-13","volume":"29","author":"Attur","year":"2015","journal-title":"Faseb j"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e0231501","DOI":"10.1371\/journal.pone.0231501","article-title":"Periostin interaction with discoidin domain receptor-1 (DDR1) promotes cartilage degeneration","volume":"15","author":"Han","year":"2020","journal-title":"PLoS One"},{"key":"B72","doi-asserted-by":"publisher","first-page":"6638","DOI":"10.1158\/0008-5472.can-06-0661","article-title":"The crucial role of cyclooxygenase-2 in osteopontin-induced protein kinase C \u03b1\/c-Src\/I\u03baB kinase \u03b1\/\u03b2\u2013Dependent prostate tumor progression and angiogenesis","volume":"66","author":"Jain","year":"2006","journal-title":"Cancer Res"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1038\/onc.2013.184","article-title":"Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via \u03b19\u03b21 integrin","volume":"33","author":"Kale","year":"2014","journal-title":"Oncogene"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2024.10066\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T04:11:44Z","timestamp":1737519104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2024.10066\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":73,"alternative-id":["10.3389\/ebm.2024.10066"],"URL":"https:\/\/doi.org\/10.3389\/ebm.2024.10066","relation":{},"ISSN":["1535-3699"],"issn-type":[{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]},"article-number":"10066"}}