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Descriptive studies suggest calcification is an organized and regulated process with many similarities to osteogenesis, yet the mechanism and its relationship to atherosclerosis remain largely unknown. In bone development and homeostasis, mineral deposition by osteoblasts and mineral resorption by osteoclasts are delicately balanced such that there is no overall gain or loss in bone mass. We hypothesize that there exists in arteries a mechanism that similarly balances mineral deposition with resorption. We propose that the cellular mediators of arterial mineral resorption are osteoclast\u2010like cells (OLCs) derived from hematopoietic precursors of the mononuclear phagocytic lineage. In arterial microenvironments, mononuclear precursors are induced to differentiate toward OLCs by macrophage\u2010colony stimulating factor and receptor activator of NF\u2010\u03baB ligand, both of which are necessary and sufficient for osteoclastogenesis and mineral resorption in bone. OLCs may participate in normal mineral homeostasis within the arterial wall or, alternatively, may be recruited to specific sites within developing plaque. Net calcium deposition occurs as a result of focal perturbation of the balance between the activity of osteoblast\u2010like cells and OLCs. Our proposed mechanism thus views arterial mineral deposition not so much as an active pathological process, but as a localized failure of protective mechanisms that actively oppose mineral deposition within the disordered metabolic milieu of developing atherosclerotic plaque.\u2014Doherty, T. M., Uzui, H., Fitzpatrick, L. A., Tripathi, P. V., Dunstan, C. R., Asotra, K., Rajavashisth, T. B. Rationale for the role of osteoclast\u2010like cells in arterial calcification.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    16, 577\u2013582 (2002)\n                  <\/jats:p>","DOI":"10.1096\/fj.01-0898hyp","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:10Z","timestamp":1027710190000},"page":"577-582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Rationale for the role of osteoclast\u2010like cells in arterial calcification"],"prefix":"10.1096","volume":"16","author":[{"given":"Terence M.","family":"Doherty","sequence":"first","affiliation":[{"name":"Atherosclerosis Research Center Division of Cardiology Department of Medicine Burns and Allen Research Institute Cedars-Sinai Medical Center and UCLA School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Uzui","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Center Division of Cardiology Department of Medicine Burns and Allen Research Institute Cedars-Sinai Medical Center and UCLA School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine A.","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Department of Internal Medicine Mayo Clinic and Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinky V.","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Center Division of Cardiology Department of Medicine Burns and Allen Research Institute Cedars-Sinai Medical Center and UCLA School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin R.","family":"Dunstan","sequence":"additional","affiliation":[{"name":"Department of Development Amgen Incorporated  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh","family":"Asotra","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Center Division of Cardiology Department of Medicine Burns and Allen Research Institute Cedars-Sinai Medical Center and UCLA School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripathi B.","family":"Rajavashisth","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Center Division of Cardiology Department of Medicine Burns and Allen Research Institute Cedars-Sinai Medical Center and UCLA School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,4]]},"reference":[{"issue":"2","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"II28","DOI":"10.1007\/s003920070097","article-title":"Natural history of calcium deposits in atherosclerosis progression and regression","volume":"89","author":"Stary H. 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