Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-11T06:06:44.617Z Has data issue: false hasContentIssue false
  • English
  • Français

The effect of bovine whey protein on ectopic bone formation in young growing rats

Published online by Cambridge University Press:  09 March 2007

Owen Kelly ,
Siobhan Cusack  and
Kevin D. Cashman
Owen Kelly
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland
Siobhan Cusack
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland
Kevin D. Cashman*
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland Department of Medicine, University College, Cork, Republic of Ireland
*
*Corresponding author:Professor Kevin D. Cashman, fax +353 21 4270244, email k.cashman@ucc.ie
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each and fed ad libitum on a semi-purified low-Ca diet (3·0 g Ca/kg diet) containing 0 (control), 10 (diet WP1) or 20 (diet WP2) g bovine WP/kg for 47 d. On day 34 of the dietary intervention, all rats had two gelatine capsules containing demineralised bone powder implanted subcutaneously in the thorax region (a well-established in vivo model of ectopic bone formation). At 14 d after implantation, alkaline phosphatase activity (reflective of bone formation) in the bone implants from animals fed WP1 and -2 diets was almost 2-fold (P<0·01) that of control animals. Insulin-like growth factor (IGF)-I mRNA levels were about 3-fold (P<0·05) higher in implants from animals fed the WP diets compared with those from control animals. Serum- and urine-based biomarkers of bone metabolism and bone mineral composition in intact femora were unaffected by WP supplementation. In conclusion, the present findings suggest that bovine WP can enhance the rate of ectopic bone formation in young growing rats fed a Ca-restricted diet. This effect may be mediated by an increased synthesis of IGF-I in growing bone. The effect of WP on bone formation warrants further investigation.

Keywords

Bone formationEctopic boneWhey proteinRats
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 3 , September 2003 , pp. 557 - 564
Copyright
Copyright © The Nutrition Society 2003

References

Ammann, P, Laib, A, Bonjour, JP, Meyer, JM, Ruegsegger, P & Rizzoli, R (2002) Dietary essential amino acid supplements increase bone strength by influencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet. J Bone Miner Res 17, 1264–1272.CrossRefGoogle ScholarPubMed
Aoe, S, Toba, Y, Yamamura, J, et al. (2001) Controlled trial of the effects of milk basic protein (MBP) supplementation on bone metabolism in healthy adult women. Biosci Biotechnol Biochem 65, 913–918.CrossRefGoogle Scholar
Ballard, FJ, Nield, MK, Francis, GL, Dahlenburg, GW & Wallace, JC (1982) The relationship between the insulin content and inhibitory effects of bovine colostrum on protein breakdown in cultured cells. J Cell Physiol 110, 249–254.CrossRefGoogle ScholarPubMed
Calabresi, E, Lasagni, L, Franceschelli, F, Bartolini, L & Serio, M (1994) Use of an internal standard to measure pyridinoline and deoxypyridinoline in urine (letter). Clin Chem 40, 336–337.CrossRefGoogle Scholar
Colwell, R, Russell, RGG & Eastell, R (1993) Factors affecting the assay of urinary 3-hydroxypyridinium cross-links of collagen as markers of bone resorption. Eur J Clin Invest 23, 341–349.CrossRefGoogle Scholar
Cox, DA & Bürk, RR (1991) Isolation and characterisation of milk growth factor, a transforming-growth-factor-beta 2-related polypeptide, from bovine milk. Eur J Biochem 197, 353–358.CrossRefGoogle ScholarPubMed
Dallal, GE (1990) PC-Size consultant – A program for sample size determinations. Am Stat 44, 243.CrossRefGoogle Scholar
DeSimone, DP & Reddi, AH (1983) Influence of vitamin A on matrix-induced endochondral bone formation. Calcif Tissue Int 35, 732–739.CrossRefGoogle ScholarPubMed
Fleet, JC, Cashman, K, Cox, K & Rosen, V (1996) The effects of aging on the bone inductive activity of recombinant human bone morphogenetic protein-2. Endocrinology 137, 4605–4610.CrossRefGoogle ScholarPubMed
Fleet, JC & Hock, JM (1994) Identification of osteocalcin mRNA in nonosteoid tissue of rats and humans by reverse transcription–polymerase chain reaction. J Bone Miner Res 9, 1565–1573.CrossRefGoogle ScholarPubMed
Francis, GL, Upton, FM, Ballard, FJ, McNeil, KA & Wallace, JC (1988) Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form. Biochem J 251, 95–103.CrossRefGoogle ScholarPubMed
Funaba, M, Kawashima, T, Yano, H & Kawashima, R (1990) Effects of a high protein diet on bone formation and calcium metabolism in rats. J Nutr Sci Vitaminol 36, 559–567.CrossRefGoogle Scholar
Hoshino, H, Kushida, K, Takahashi, M, Koyama, S, Yamauchi, H & Inoue, T (1998) Effects of low phosphate intake on bone and mineral metabolism in rats: evaluation by biochemical markers and pyridinium cross-link formation in bone. Ann Nutr Metab 42, 110–118.CrossRefGoogle Scholar
Ito, T (1991) Science of breast milk. New Food Industry 33, 73–80.Google Scholar
Kalu, DN, Liu, CC, Salerno, E, Hollis, B, Echon, R & Ray, M (1991) Skeletal response of ovariectomized rats to low and high doses of 17 beta-estradiol. Bone Miner 14, 175–187.CrossRefGoogle ScholarPubMed
Kimura, T, Murakawa, Y, Ohno, M, Ohtani, S & Higaki, K (1997) Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats. J Pharmacol Exp Ther 283, 611–618.Google ScholarPubMed
Lowry, OH, Rosebrough, NJ, Farr, AL & Randall, RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265–275.CrossRefGoogle ScholarPubMed
Matsui, T, Yano, H, Awano, T, Harumoto, T & Saito, Y (1994) The influences of casein phosphopeptides on metabolism of ectopic bone induced by decalcified bone matrix implantation in rats. J Nutr Sci Vitaminol 40, 137–145.CrossRefGoogle ScholarPubMed
Philipps, AF, Dvorak, B, Kling, PJ, Grille, JG & Koldovsky, O (2000) Absorption of milk-borne insulin-like growth factor-I into portal blood of suckling rats. J Pediatr Gastroenterol Nutr 31, 128–135.Google ScholarPubMed
Philipps, AF, Kling, PJ, Grille, JG & Dvorak, B (2002) Intestinal transport of insulin-like growth factor-I (IGFI) in the suckling rat. J Pediatr Gastroenterol Nutr 35, 539–544.Google ScholarPubMed
Porter, KH & Johnson, MA (1998) Dietary protein supplementation and recovery from femoral fracture. Nutr Rev 56, 337–340.CrossRefGoogle ScholarPubMed
Price, JS, Oyajobi, BO & Russell, RG (1994) The cell biology of bone growth. Eur J Clin Nutr 48, S131–S149.Google ScholarPubMed
Reeves, PG, Nielsen, FH & Fahey, GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123, 1939–1951.CrossRefGoogle Scholar
Robins, SP, Stead, DA & Duncan, A (1994) Precautions in using an internal standard to measure pyridinoline and deoxypyridinoline in urine (letter). Clin Chem 40, 2322–2323.CrossRefGoogle Scholar
Rodan, GA & Rodan, SB (1995) The cells of bone. In Osteoporosis: Etiology, Diagnosis, and Management, 2nd ed. pp. 1–39 [Riggs, BL and Melton, LJ III, editors]. Philadelphia, PA: Lippincot-Raven.Google Scholar
Schurch, MA, Rizzoli, R, Slosman, D, Vadas, L, Vergnaud, P & Bonjour, JP (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128, 801–809.CrossRefGoogle ScholarPubMed
Schwartz, R & Reddi, AH (1979) Influence of magnesium depletion on matrix-induced endochondral bone formation. Calcif Tissue Int 29, 15–20.CrossRefGoogle ScholarPubMed
Sinha, R, Smith, JC Jr & Soares, JH Jr (1988 a) Calcium and vitamin D in bone metabolism: analyses of their effects with a short-term in vivo bone model in rats. J Nutr 118, 99–106.CrossRefGoogle ScholarPubMed
Sinha, R, Smith, JC & Soares, JH (1988 b) The effect of dietary calcium on bone metabolism in young and aged female rats using a short-term in vivo model. J Nutr 118, 1217–1222.CrossRefGoogle Scholar
Snedecor, GW & Cochran, WG (1967) Statistical Methods. Ames, IA: Iowa State University Press.Google Scholar
Takada, Y, Aoe, S & Kumegawa, M (1996) Whey protein stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 223, 445–449.CrossRefGoogle ScholarPubMed
Takada, Y, Kobayashi, N, Kato, K, Matsuyama, H, Yahiro, M & Aoe, S (1997 a) Effects of whey protein on calcium and bone metabolism in ovariectomized rats. J Nutr Sci Vitaminol 43, 199–210.CrossRefGoogle ScholarPubMed
Takada, Y, Kobayashi, N, Matsuyama, H, et al. (1997 b) Whey protein suppresses the osteoclast-mediated bone resorption and osteoclast cell formation. Int Dairy J 7, 821–825.CrossRefGoogle Scholar
Takada, Y, Matsuyama, H, Kato, K, et al. (1997 c) Milk whey protein enhances the bone breaking force in ovariectomized rats. Nutr Res 17, 1709–1720.CrossRefGoogle Scholar
Toba, Y, Takada, Y, Matsuoka, Y, et al. (2001) Milk basic protein promotes bone formation and suppresses bone resorption in healthy adult men. Biosci Biotechnol Biochem 65, 1353–1357.CrossRefGoogle ScholarPubMed
Toba, Y, Takada, Y, Yamamura, J, et al. (2000) Milk basic protein: a novel protective function of milk against osteoporosis. Bone 27, 403–408.CrossRefGoogle ScholarPubMed
Weiss, RE, Gorn, A, Dux, S & Nimni, ME (1981) Influence of high protein diets on cartilage and bone formation in rats. J Nutr 111, 804–816.CrossRefGoogle ScholarPubMed
Weissman, N & Pileggi, VJ (1974) Inorganic ions. In Clinical Chemistry: Principles and Techniques, pp. 639–755 [Henry,, RJ, Cannon, DC and Winkelman, JW, editors]. Hagers-town, MD: Harper and Row.Google Scholar
Yakar, S, Rosen, CJ, Beamer, WG, et al. (2002) Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110, 771–781.CrossRefGoogle ScholarPubMed
Yamamura, J, Takada, Y, Goto, M, Kumegawa, M & Aoe, S (1999) High mobility group-like protein in bovine milk stimulates the proliferation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 261, 113–117.CrossRefGoogle ScholarPubMed