Immunohistochemical localization of bone morphogenetic proteins (BMPs) 2, 4, 6, and 7 during induced heterotopic bone formation.
The distribution and staining intensity of bone morphogenetic proteins (BMPs) 2, 4, 6, and 7 were assessed by immunohistochemistry in ectopic bone induced in Nu/Nu mice by Saos-2 cell derived implants. Devitalized Saos-2 cells or their extracts can induce endochondral bone formation when implanted subcutaneously into Nu/Nu mice. BMP staining was mostly cytoplasmic. The most intense BMP staining was seen in hypertrophic and apoptotic chondrocytes, osteoprogenitor cells such as periosteal and perivascular cells, and osteoblasts. BMP staining in osteocytes and osteoclasts was variable, ranging from undetectable to intensely stained, and from minimal to moderately stained in megakaryocytes of the induced bone marrow. BMP-2, 4, 6, and 7 staining in Saos-2 implant-induced bone indicates the following: (1) Saos-2 cell products promote expression of BMPs by host osteoprogenitor cells, which in turn, leads to bone and marrow formation at ectopic sites; (2) strong BMP staining is seen in maturing chondrocytes, and thus may play a role in chondrocyte differentiation and/or apoptosis; (3) BMP expression in perivascular and periosteal cells indicates that osteoprogenitor cells also express BMP; (4) BMP release by osteoclasts may promote osteoblastic differentiation at sites of bone remodeling. These new data can be useful in understanding the role of BMPs in promoting clinical bone repair and in various pathologic conditions.
McCullough
Kirk A
KA
Departments of Pathology and Laboratory Medicine and Orthopedic Surgery, Bone Research Lab, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, Kansas 66160, USA.
Waits
Chad A
CA
Garimella
Rama
R
Tague
Sarah E
SE
Sipe
Joseph B
JB
Anderson
H Clarke
HC
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D002828:Choristoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; C525819:BMP7 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta