title: The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials.
abstract: Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that appears to be derived primarily from the liver and delivered to other tissues in a protective complex. A significant role in bone growth and turnover is suggested by genetic studies that associate the gene locus (SPP2) with bone mineral density and bone quality. The function of this protein in the normal bone environment is unknown but clues are given by the fact that Spp24, or proteolytic products of Spp24, bind cytokines of the TGF-β superfamily and also activate intracellular signaling pathways. Several potential biotherapeutics have been engineered from this protein including materials that enhance BMP-induced bone healing and, on the other hand, materials that inhibit BMPs in clinical situations where this is called for such as reducing BMP-induced inflammation and inhibiting tumors dependent on BMP autocrine systems. As understanding of the structure and function of this protein increases, more opportunities for rationally developed therapeutics will become apparent.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Sepulveda Ambulatory Care Center, VA Greater Los Angeles, and Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Samuel.Murray@va.gov.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
authors.affiliation: Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: National Institute of Traumatology and Orthopaedics (INTO) and Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Maria Eugenia Leite
authors.initials: ME
authors.lastname: Duarte
authors.affiliation: Research Service, VA Greater Los Angeles, Los Angeles, CA, USA.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, PRC.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.affiliation: Business Development Group, Coventry University, Coventry, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Francis
authors.affiliation: Geriatric Research, Education, and Clinical Center, Sepulveda Ambulatory Care Center, VA Greater Los Angeles, and Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
authors.forename: Elsa J
authors.initials: EJ
authors.lastname: Brochmann Murray
mesh_terms: D000818:Animals; D015519:Bone Density; D001857:Bone Matrix / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D002417:Cattle; D002642:Chick Embryo; D016207:Cytokines / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D010024:Osteoporosis; D010750:Phosphoproteins / Q000502:physiology* / Q000627:therapeutic use; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D010750:Phosphoproteins; C551869:SPP2 protein, human; C000605935:SPP2 protein, mouse; D016212:Transforming Growth Factor beta; C091340:secreted phosphoprotein 24