Abstract
Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.
Similar content being viewed by others
References
Garcia-Carrasco M, Gruson M, de Vernejoul MC, Denne MA, Miravet L (1988) Osteocalcin and bone morphometric parameters in adults without bone disease. Calcif Tissue Int 42:13–17
Kelly PJ, Pocock NA, Sambrook PN, Eisman JA (1989) Age-and menopause-related changes in indices of bone turnover. J Clin Endocrinol Metab 69:1160–1165
Sontag W (1986) Quantitative measurements of periosteal and cortico-endosteal bone formation and resorption in the midshaft of female rat femur. Bone 7:55–62
Aloia JF, Vaswani A, Meunier PJ, Edouard CM, Arlot ME, Yeh JK, Cohn SH (1987) Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin. Calcif Tissue Int 40:253–259
Florini JR, Prinz PN, Vitiello MV, Hintz RL (1985) Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol 40:2–7
Lindsay R, Aitken JM, Anderson JB, Hart DM, MacDonald EB, Clark AC (1976) Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1:1038–1041
Sontag WE, Steger RW, Forman LJ, Meites J (1980) Decreased pulsatile release of growth hormone in old male rats. Endocrinology 107:1875–1879
Weiss NS, Ure CL, Ballard JH, William AR, Dailing JR (1980) Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 303:1195–1198
Bak B, Andreassen TT (1989) The effect of aging on fracture healing in the rat. Calcif Tissue Int 45:292–297
Irving JT, LeBolt SA, Schneider EL (1981) Ectopic bone formation and aging. Clin Orthop Rel Res 154:249–253
Nishimoto SK, Chang CH, Gendler E, Stryker WF, Nimni ME (1985) The effect of aging on bone formation in rats: biochemical and histological evidence for decreased bone formation capacity. Calcif Tissue Int 37:617–624
Howes R, Bowness JM, Grotendorst GR, Martin GR, Reddi AH (1988) Platelet-derived growth factor enhances demineralized bone matrix-induced cartilage and bone formation. Calcif Tissue Int 42:34–38
Liang CT, Barnes J, Seeder JG, Quartuccio HA, Bolander M, Jeffrey JJ, Rodan GA (1992) Impaired bone activity in aged rats: alterations at the celluler and molecular levels. Bone 13:435–441
Oghushi H, Goldberg VM, Caplan AI (1989) Heterotropic osteogenesis in porous ceramics induced by marrow cells. J Orhtop Res 7:568–578
Goshima J, Goldberg VM, Caplan AI (1991) The osteogenic potential of culture-expanded rat marrow stromal cells assayed in vivo in calcium phosphate ceramic blocks. Clin Orthop Rel Res 262:298–311
Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88
Tsuji T, Hughes FJ, McCulloch CAG, Melcher AH (1990) Effects of donor age on osteogenic cells of rat bone marrow in vitro. Mech Aging Dev 51:121–132
Egrise D, Martin D, Neve P, Verhas M, Schoutens A (1992) Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats. Calcif Tissue Int 50:336–347
Noda M, Yoon K, Thiede M, Buenaga R, Weiss M, Henthorn P, Harris H, Rodan GA (1987) cDNA cloning of alkaline phosphatase from rat osteosarcoma (ROS 17/2.8) cells. J Bone Miner Res 2:161–164
Genovese C, Rowe D, Kream B (1984) Construction of DNA sequences complementary to rat α1 and α2 collagen mRNA and their use in studying the regulation of type I collagen synthesis by 1,25-dihydroxyvitamin D. Biochemistry 23:6210–6216
Weinreb M, Shinar D, Rodan GA (1990) Different pattern of alkaline phosphatase, osteopontin and osteocalcin expression in developing rat bone visualized by in situ hybridization. J Bone Miner Res 8:831–842
Yoon K, Buenaga R, Rodan GA (1987) Tissue specificity and developmental expression of rat osteopontin. Biochem Biophys Res Comm 148:1129–1136
Hollander MC, Fornace AJ Jr (1990) Estimation of relative mRNA content by filter hybridization to a polythymidylate probe. Biotechniques 9:174–179
Friedenstein AJ (1976) Precursor cells of mechanocytes. Int Rev Cytol 47:327–359
Maniatopoulos C, Sodek J, Melcher AH (1988) Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res 254:413–330
Owen ME, Cave J, Joyner CJ (1987) Clonal analysis in vitro of osteogenic differentiation of marrow stromal CFU-F. J Cell Sci 87:731–738
Leboy PS, Beresford JN, Devlin C, Owen ME (1991) Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures. J Cell Physiol 146:370–378
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Quarto, R., Thomas, D. & Liang, C.T. Bone progenitor cell deficits and the age-associated decline in bone repair capacity. Calcif Tissue Int 56, 123–129 (1995). https://doi.org/10.1007/BF00296343
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00296343