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Specifically, studies in murine models of structural allograft healing demonstrated that rPTH treatment increased angiogenesis (vessels &amp;lt;30\u2009\u03bcm), and decreased arteriogenesis (&amp;gt;30\u2009\u03bcm) and mast cell numbers, which lead to decreased fibrosis and accelerated healing. To better understand these non-anabolic effects, we interrogated osteogenesis, vasculogenesis, and mast cell accumulation in mice randomized to placebo (saline), rPTH (20\u2009\u03bcg\/kg\/2 days), or the mast cell inhibitor sodium cromolyn (SC) (24\u2009\u03bcg\/kg\/ 2days), via longitudinal micro\u2013computed tomography (\u03bcCT) and multiphoton laser scanning microscopy (MPLSM), in a critical calvaria defect model. \u03bcCT demonstrated that SC significantly increased defect window closure and new bone volume versus placebo (p\u2009&amp;lt;\u20090.05), although these effects were not as great as rPTH. Interestingly, both rPTH and SC have similar inhibitory effects on arteriogenesis versus placebo (p\u2009&amp;lt;\u20090.05) without affecting total vascular volume. MPLSM time-course studies in untreated mice revealed that large numbers of mast cells were detected 1 day postoperation (43\u2009\u00b1\u200917), peaked at 6 days (76\u2009\u00b1\u20096), and were still present in the critical defect at the end of the experiment on day 30 (20\u2009\u00b1\u200912). In contrast, angiogenesis was not observed until day 4, and functional vessels were first observed on 6 days, demonstrating that mast cell accumulation precedes vasculogenesis. To confirm a direct role of mast cells on osteogenesis and vasculogenesis, we demonstrated that specific diphtheria toxin-\u03b1 deletion in Mcpt5-Cre-iDTR mice results in similar affects as SC treatment in WT mice. Collectively, these findings demonstrate that mast cells inhibit bone defect healing by stimulating arteriogenesis associated with fibrotic scaring, and that an efficacious non-anabolic effect of rPTH therapy on bone repair is suppression of arteriogenesis and fibrosis secondary to mast cell inhibition. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3178","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T05:55:28Z","timestamp":1496123728000},"page":"1870-1883","source":"Crossref","is-referenced-by-count":35,"title":["Teriparatide Treatment Improves Bone Defect Healing Via Anabolic Effects on New Bone Formation and Non-Anabolic Effects on Inhibition of Mast Cells in a Murine Cranial Window Model"],"prefix":"10.1093","volume":"32","author":[{"given":"Longze","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of OrthopaedicsUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Biomedical EngineeringUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Biomedical EngineeringUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Department of OrthopaedicsUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"},{"name":"Center for Musculoskeletal ResearchUniversity of Rochester School of Medicine and DentistryRochesterNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,30]]},"reference":[{"issue":"4","key":"2024021014195128300_jbmr3178-bib-0001","doi-asserted-by":"crossref","first-page":"00062","DOI":"10.2106\/JBJS.RVW.M.00062","article-title":"Treatment of traumatic segmental long-bone defects: a critical analysis review","volume":"2","author":"Molina","year":"2014","journal-title":"JBJS Rev"},{"issue":"6","key":"2024021014195128300_jbmr3178-bib-0002","first-page":"1117","article-title":"Teriparatide therapy as an adjuvant for tissue engineering and integration of biomaterials","volume":"4","author":"Dhillon","year":"2011","journal-title":"J Mater Res"},{"issue":"19","key":"2024021014195128300_jbmr3178-bib-0003","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone 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