Subscribe to RSS
DOI: 10.1055/s-0038-1632497
Effects of a Bone Inducing Agent Derived from a Cultured Human Osteosarcoma Cell Line after Orthotopic and Heterotopic Implantation in the Dog
Publication History
Received for publication 15 April 1995
Publication Date:
10 February 2018 (online)
Summary
BIA, a Bone Inducing Agent extracted from a cultured human osteosarcoma cell line (Saos–2), is highly osteoinductive in the skeletal muscle of athymic mice and promotes early osseous union of stabilized femoral non-unions in rats. To evaluate its effect in dogs, ten milligrams of BIA mixed with an equal amount of pure bovine collagen type I was compared with 20 mg of bovine collagen alone, a gelatin capsule alone, and fresh autogenous cancellous graft, after orthotopic and heterotopic implantation in Beagles.
For osteoinductive bioassays, each implant was placed in the latissimus dorsi muscle of five Beagles for six weeks. Bone formation was evaluated by thoracic radiographs every two weeks and by high detail radiographs and histology six weeks after implantation. To evaluate the effects of BIA after orthotopic implantation, four cortical defects were created in each left femur of four Beagles. One defect on each femur was randomly filled with BIA plus collagen, collagen alone, a gelatin capsule alone, or autogenous cancellous graft. Radiographic evaluation of the femurs was performed every two weeks for eight weeks. Healing of the defects was assessed with high detail radiographs, dual energy X-ray absorptiometry, histology and histomorphometry eight weeks after implantation.
Ten mg of BIA did not induce bone formation six weeks after heterotopic implantation and did not promote bone healing after orthotopic implantation in the dogs. The discrepancy between these results and those obtained in rodents may be related to immunogenic factors or to the dose of BIA used in this study.
BIA, a Bone Inducing Agent extracted from a cultured osteosarcoma cell line is highly osteoinductive in rodents. BIA was evaluated and compared with autogenous cancellous bone graft and bovine collagen after orthotopic and heterotopic implantation in Beagles. Each implant was placed in the latissimus dorsi muscle of five Beagles and in femoral cortical defects of four Beagles. Bone formation was evaluated by radiography, dual energy X-ray absorptiometry, histology and histo-morphometry. BIA did not induce bone formation after heterotopic implantation and did not promote bone healing after orthotopic implantation in dogs.
-
REFERENCES
- 1 Alexander JW. Bone grafting. Vet Clin North Am: Small Anim Pract 1987; 17 (04) 811-19.
- 2 Fox SM. Cancellous bone grafting in the dog: an overview. J Am Anim Hosp Assoc 1984; 20: 840-48.
- 3 Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapatite as a bone-graft substitute in metaphyseal defects. J Bone Joint Surg 1986; 68 A (06) 904-11.
- 4 Rose PL, Auer JA, Hulse D, Hightower D, Schenk RK. Effects of β-Tricalcium phosphate in surgically created subchondral bone defects in male horses. Am J Vet Res 1988; 49: 417-24.
- 5 Sauk JJ, Van Kampen CL. Use of a phosphoryn-Ca2+-collagen composition that mimics a mineralization front in unicortical defects in long bones. J Biomed Mater Res 1991; 25: 609-20.
- 6 Urist MR, DeLange RJ, Finerman GAM. Bone cell differentiation and growth factors. Science 1983; 220: 680-6.
- 7 Forell EB, Straw RC. Bone morphogenetic proteins and bone derived growth factors. VCOT 1993; 6: 166-71.
- 8 Anderson HC. Recent advances in methods for inducing bone formation. Curr Opin Ther Patents 1994; 4 (01) 17-29.
- 9 Wozney JM, Rosen V, Celeste AJ. et al Novel regulators of bone formation: molecular clones and activities. Science 1988; 242: 1528-34.
- 10 Yasko AW, Lane JM, Fellinger EJ. et al The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological and biomechanical study in rats. J Bone Joint Surg 1992; 74 A 659-70.
- 11 Kirker-Head CA. Recombinant bone morphogenetic proteins: novel substances for enhancing bone healing. Vet Surg 1995; 24: 408-19.
- 12 Cook SD, Baffes GC, Wolfe MW. et al Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. Clin Orthop Rel Res 1994; 301: 302-12.
- 13 Anderson HC, Hsu HH, Raval P. et al The mechanism of bone induction and bone healing by human osteosarcoma cell extracts. Clin Orthop Rel Res 1995; 313: 129-34.
- 14 Urist MR, Chang JJ, Lietze A. et al Preparation and bioassay of bone morphogenetic protein and polypeptides fragments. Methods Enzymol 1987; 146: 294-312.
- 15 Bolander ME, Balian G. The use of demineralized bone matrix in the repair of segmental defects. Augmentation with extracted matrix proteins and a comparison with autologous grafts. J Bone Joint Surg 1986; 68 A 1264-74.
- 16 Johnson EE, Urist MR, Finerman GA. Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone. Clin Orthop Rel Res 1992; 277: 229-37.
- 17 Hopp SG, Dahners LE, Gilbert JA. A study of the mechanical strength of long bone defects treated with various bone autograft substitutes: an experimental investigation in the rabbit. J Orthop Res 1989; 7: 579-84.
- 18 Wozney JM. Bone morphogenetic proteins and their gene expression. In: Cellular and Molecular Biology of Bone. Masaki Noda, ed. Tokyo: Academic Press, Inc; 1993: 131-67.
- 19 Anderson HC, Sugamoto K, Morris DC. et al Bone inducing agent (BIA) from cultured human Saos-2 osteosarcoma cells. Bone Miner 1992; 16: 49-62.
- 20 Hunt TR, Schwappach J, Hsu HHT. et al Repair of a segmental defect in the rat femur using a bone inducing agent (BIA) derived from cultured human Saos-2 osteosarcoma. Trans Orthop Res Soc 1993; 18: 489
- 21 Fogh J, Trempe G. New human tumor cell lines. In: Human Tumor Cells in Vitro. Fogh J. (ed.) New York: Plenum Press; 1975: 115-59.
- 22 Johnson KA. Histologic features of the healing of bone graft donor sites in dogs. Am J Vet Res 1988; 49 (06) 885-8.
- 23 Takaoka K, Yoshikawa H, Hashimoto J. et al Purification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type). Clin Orthop Rel Res 1993; 292: 329-36.
- 24 Yan J, Lianjia Y. The relationship between bone morphogenetic protein and neoplastic diseases. Clin Orthop Rel Res 1990; 259: 233-8.
- 25 Htakeyama S, Ohara-Nemoto Y, Kyakumoto S, Satoh M. Expression of bone morphogenetic in human adenocarcinoma cell line. Biochem Biophys Res Commun 1993; 190: 695-701.
- 26 Takaoka K, Yoshikawa H, Masuhara K. et al Establishment of a cell line producing bone morphogenetic protein from a human osteosarcoma. Clin Orthop Rel Res 1989; 244: 258-64.
- 27 Raval P, Hsu HHT, Harris S, Moylan S, Chen M, Anderson HC. Expression of bone morphogenetic proteins and transforming growth factor beta in osteoinductive Saos-2 cells. Trans Orthop Res Soc 1993; 18: 180
- 28 Miyamoto S, Takaoka K, Ono K. Bone induction in monkeys by bone morphogenetic protein. A transfilter technique. J Bone Joint Surg 1993; 75 B 107-10.
- 29 Sato K, Urist MR. Induced regeneration of calvaria by bone morphogenetic protein (BMP) in dogs. Clin Orthop Rel Res 1985; 197: 301-11.
- 30 Coulson RA. Relationship between fluid flow and O2demand in tissues in vivo and in vitro. Perspect Biol Med 1983; 27: 121
- 31 Nade S. Clinical implications of cell function in osteogenesis. A reappraisal of bone-graft surgery. Annals of the Royal College of Surgeons of England 1979; 61: 189-94.
- 32 Chalmers J, Gray DH, Rush J. Observations on the induction of bone in soft tissues. J Bone Joint Surg 1975; 57 B 36-45.
- 33 Trevor PB, Stevenson S, Carrig CB, Waldron DR, Smith MM. Evaluation of biocompatible osteoconductive polymer as an orthopedic implant in dogs. J Am Vet Med Assoc 1992; 200: 1651-60.
- 34 Howard PE, Wilson JW, and Ribble GA. Effects of gelatin sponge implantation in cancellous bone defects in dogs. J Am Vet Med Assoc 1988; 192: 633-7.
- 35 Elkins AD, and Jones LP. The effects of plaster of Paris and autogenous cancellous bone on the healing of cortical defects in the femurs of dogs. Vet Surg 1988; 17 (02) 71-6.
- 36 Bessho K, Iizuka T. Activity and solubility of bone morphogenetic protein derived from porcine bone matrix. Br J Oral Maxillofac Surg 1994; 32: 86-90.
- 37 Gao TJ, Lindholm TS, Marttinen A, Puolakka T. Bone inductive potential and dose-dependent response of bovine bone morphogenetic protein combined with type IV Collagen carrier. Ann Chirurgiae Gynaecologiae 1993; 82: 77-84.
- 38 Aspenberg P, Lohmander LS, Thorngren KG. Monkey bone matrix induces bone formation in the athymic rat, but not in adult monkeys. J Orthop Res 1991; 9: 20-5.
- 39 Nade S, Burwell G. Decalcified bone as a substrate for osteogenesis. An appraisal of the interrelation of bone and marrow in combined grafts. J Bone Joint Surg 1977; 59 B 189-96.
- 40 Nilsson OS, Urist MR, Dawson EG, Schmalzried TP, Finerman GA. Bone repair induced by bone morphogenetic protein in ulnar defects in dogs. J Bone Joint Surg 1986; 68 B 635-42.
- 41 Vail TB, Trotter GW, Powers BE. Equine demineralized bone matrix: relationship between particle size and osteoinduction. Vet Surg 1994; 23: 386-95.
- 42 Forell EB, Straw RC, Powers BE. et al Evaluation of the osteoinductive capacity of canine demineralized bone matrix in heterotopic muscle sites of athymic rats. VCOT 1993; 6: 21-8.
- 43 Aspenberg P, Wang E, Thorngren KG. Bone morphogenetic protein induces bone in the squirrel monkey, but bone matrix does not. Acta Orthop Scand 1992; 63: 619-22.
- 44 Nillsson OS, Urist MR. Immune inhibition of repair of canine skull trephine defects implanted with partially purified bovine morphogenetic protein. Int Orthop 1991; 15: 257-63.
- 45 Lindholm TC, Lindholm TS, Marttinen A, Urist MR. Bovine bone morphogenetic protein (bBMP/NCP) induced repair of skull trephine defects in pigs. Clin Orthop Rel Res 1994; 301: 262-70.
- 46 Sampath TK, AH Reddi. Homology of boneinductive proteins from human, monkey, bovine, and rat extracellular matrix. Proc Natl Acad Sci USA 1983; 80: 6591-5.
- 47 Bessho K, Tagawa T, Murata M. Comparison of bone matrix-derived bone morphogenetic proteins from various animals. J Oral Maxillofac Surg 1992; 50: 496-501.