Summary
The role of transforming growth factor β (TGF-β) in fracture healing has previously been investigated in a rodent model, but not in human material. We investigated TGF-β1 gene expression in specimens of callus from normally healing human fractures, using in situ hybridization to a cDNA TGF-β1 probe and an autoradiographic disclosure system. TGF-β1 mRNA was present in areas of proliferation of mesenchymal tissue, bone, and cartilage. Levels of expression were lower in cells in the fracture hematoma and in differentiated (hypertrophic) chondrocytes. These results are compatible with those found in various animal models using immunohistochemistry and support the view that locally produced TGF-β1 is a regulator of fracture repair in humans from the early (mesenchymal proliferation) stage to the stage of remodeling of woven bone. They also indicate that, for TGF-β1, animal models accurately reflect human bone repair.
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References
Joyce ME, Jingushi S, Scully SP, Bolander ME (1991) Role of growth factors in fracture healing. Prog Clin Biol Res 365: 391–416
Joyce ME, Jingushi S, Bolander ME (1990) Transforming growth factor-beta in the regulation of fracture repair. Orthop Clin North Am 21: 199–209
Joyce ME, Roberts AB, Sporn MB, Bolander, ME (1990) Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 110: 2195–2207
Urist MR, Johnson R (1943) Calcification and ossification. 4. The healing of fractures in man under clinical conditions. J Bone Joint Surg 25: 375–426
Charnley J (1950) Fracture treatment. In: Platt H (eds) Modern trends in orthopaedics. Butterworth, London, P 534
Collins DH (1966) Pathology of bone. Butterworth, London
Sevitt S (1981) Bone repair and fracture healing in man, Churchill Livingstone, Edinburgh
Jundt G, Berghauser KH, Termine JD, Schulz A (1987) Osteonectin—a differentiation marker of bone cells. Cell Tissue Res 248: 409–415
Marles PJ, Hoyland JA, Parkinson R, Freemont AJ (1991) Demonstration of variation in chondrocyte activity in different zones of articular cartilage: an assessment of the value of in situ hybridisation. Int J Exp Pathol 72: 171–182
Hoyland JA, Thomas JT, Donn R, Marriott A, Ayad S, Boot-Handford RP, Grant ME, Freemont AJ (1991) Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage. Bone Miner 15: 151–164
Noda M, Rodan GA (1989) Type beta transforming growth factor regulates expression of gene encoding bone matrix proteins. Connect Tissue Res 21: 71–75
Centrella M, McCarthy TL, Canalis E (1989) Effects of transforming growth factors on bone cells. Connect Tissue Res 20: 267–275
Centrella M, McCarthy TL, Canalis E (1991) Transforming growth factor and remodelling of bone. J Bone Joint Surg 73A: 1418–1428
Whitby DJ, Ferguson MW (1991) Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol 147: 207–215
Kane CJ, Hebda PA, Mansbridge JN, Hanawalt PC (1991) Direct evidence for spatial and temporal regulation of transforming growth factor beta 1 expression during cutaneous wound healing. J Cell Physiol 148: 157–173
Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79: 319–326
Rappolee DA, Mark D, Banda MJ, Werb Z (1988) Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science 241: 708–712
Thorp B, Anderson I, Jakowlew S (1992) Transforming growth factor β1, β2 and β3 in cartilage and bone cells during endochondral ossification in the chick. Development 114: 907–911
Hunt TK, Knighton DR, Thakral KK, Goodson WH, Andrews WS (1984) Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 96: 48–54
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Andrew, J.G., Hoyland, J., Andrew, S.M. et al. Demonstration of TGF-β1 mRNA by in situ hybridization in normal human fracture healing. Calcif Tissue Int 52, 74–78 (1993). https://doi.org/10.1007/BF00308311
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DOI: https://doi.org/10.1007/BF00308311