Human skeletal growth factor: characterization of the mitogenic effect on bone cells in vitro

Farley,; Masuda, Takeshi; Je, Wergedal; Baylink, D J

doi:10.1021/bi00257a038

Cited by 49 publications

(10 citation statements)

References 14 publications

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“…A substance referred to as human skeletal growth factor has been isolated from human bone and shown to increase DNA synthesis in bone cells, stimulate osteoblast proliferation, and induce bone formation [ 65 ]. Similar and possibly identical factors are present in bone from other species [63].…”

Section: Reversalmentioning

confidence: 99%

The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone

1984

Calcif Tissue Int

364

167

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The cellular basis of the normal bone remodeling sequence in the human adult is discussed in relation to a cycle of five stages--quiescence, activation, resorption, reversal, formation, and return to quiescence. Normally, 80% or more of free bone surfaces are quiescent with respect to remodeling. The structure of the quiescent surface comprises 5 layers; listed in order out toward the bone marrow these are: the lamina limitans (the electron dense outer edge of the mineralized bone matrix), unmineralized connective tissue that may be confused with osteoid by light microscopy, flattened lining cells of osteoblast lineage separated by narrow gaps, more unmineralized connective tissue, and finally either the squamous sac cells of red marrow or the cytoplasm of fat cells of yellow marrow. Activation requires the recruitment of new osteoclasts derived from precursor cells of the mononuclear phagocyte system (and so ultimately from the hematopoietic stem cell), a method for precursor cells to penetrate the cellular and connective tissue barrier of the quiescent surface, and so gain access to the bone mineral, and mechanisms for their attraction and binding to the mineralized surface, possibly in response to chemotactic signals released from bone matrix or mineral. Each of these three steps is probably mediated in some way by lining cells. Resorption is carried out by osteoclasts, most of which are multinucleated. The mean life span of individual nuclei is about 12.5 days; the additional nuclei needed to sustain resorption may be derived from local as well as blood-bone precursors, but nothing is known of their fate.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Reversalmentioning

confidence: 99%

The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone

1984

Calcif Tissue Int

364

167

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“…In addition, skeletal growth factor and transforming growth factor-,3-like activity were found in extracts of bovine bone matrix (25) and skeletal growth factor was present in abstracts of human bone (24). The component(s) responsible for the mitogenic activity in DABM in the present studies has not been identified.…”

Section: Discussionmentioning

confidence: 59%

Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats.

Turner¹,

Farley²,

Vandersteenhoven³

et al. 1988

J. Clin. Invest.

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Osteoinduction is the formation of ectopic bone that follows implantation of demineralized allogeneic bone matrix (DABM) and is believed to be secondary to the release of associated inductive factors from bone matrix. To clarify the role of vitamin D in osteoinduction, we implanted DABM from vitamin D-deficient rats (-D rats) into normal rats (+D rats). Because mitogens and osteocalcin might be involved in osteoinduction, these were measured. Mitogenic activity in extracts from mineralized allogeneic bone matrix (ABM) and DABM from both +D and -D rats was determined with an assay that utilizes monolayer cultures of embryonic chick calvarial cells. Osteocalcin in serum and DABM was measured by radioimmunoassay. DABM from -D rats did not promote osteoinduction as effectively as DABM from +1 rats. Resorption of implant matrix from -D rats was diminished compared with resorption of matrix from +D rats (P < 0.01), and the decrease was attributed to a corresponding decrease in the number of osteoclasts in the implants (P < 0.02). Bone formation (P < 0,01) and total implant mineralization (P < 0.001) were significantly reduced in implants from -D rats, and the reductions corresponded with a decline in the number of osteoblasts (P < 0.05). Mitogenic activity in DABM from +D rats was only slightly decreased as compared with activity in ABM, but DABM from -D rats contained significantly less activity (P < 0.001). No mitogenic activity was identified in implants of DABM from either +D or -D rats 3 wk after implantation. Serum osteocalcin was significantly higher in -D as compared with +D animals. In contrast, the concentrations of osteocalcin in DABM from the two groups of animals were not significantly different from each other. These findings indicate that the diminished osteoinductive activity of DABM from -D rats results from deficiency of one or more mitogenic factors that are essential for inducing the proliferation and differentiation of bone cells at the implant site and that osteocalcin does not play a role in this regard.

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“…Skeletal growth factor is a high molecular weight protein isolated from adult bones of human and several other species such as bovine, porcine, rat, and chick [10][11][12]. Human skeletal growth factor, purified by nondenaturing polyacrylamide gel electrophoresis, was found to have an apparent molecular weight of 83,000 daltons.…”

Section: Properties Of Hsgf: Chemical and Biologicalmentioning

confidence: 99%

“…Its activity is sensitive to trypsin and resistant to inactivation by heat, extremes of pH, collagenase, and reducing agents [10]. It stimulated DNA synthesis several hours after its addition to quiescent cells [ 11 ]. Human skeletal growth factor has been found to stimulate 3H-thymidine incorporation in mesodermal cells: cultured chick embryo bone cells and cartilage cells, human bone cells and skin cells, osteosarcoma cells, chick embryo skin cells, and Balb/C 3T3 cells [12].…”

Section: Properties Of Hsgf: Chemical and Biologicalmentioning

confidence: 99%

“…Human skeletal growth factor has been found to stimulate 3H-thymidine incorporation in mesodermal cells: cultured chick embryo bone cells and cartilage cells, human bone cells and skin cells, osteosarcoma cells, chick embryo skin cells, and Balb/C 3T3 cells [12]. No stimulation was observed in cultured kidney, muscle, or liver cells isolated from 17 day chick embryos [ 11 ]. In addition to stimulating proliferation in cultured cells, hSGF also increased 3H-proline incorporation (determined as hydroxyproline) into collagen in organ-cultured chick embryo tibiae or calvariae [ I I ].…”

Section: Properties Of Hsgf: Chemical and Biologicalmentioning

confidence: 99%

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Bone-derived factors active on bone cells

et al. 1984

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Effects of systemic calcium regulating hormones have been studied extensively, yet mechanisms of bone volume regulation at the local level are poorly understood. Our laboratory has reported evidence for two locally mediated processes of bone volume regulation which function independently of systemic control: (1) coupling of bone formation and resorption and (2) repletion of resorbed bone. These local regulatory mechanisms have been shown to occur in vivo and in vitro. We have reported that embryonic chick tibiae in culture, stimulated to resorb, release a factor in the serum-free culture medium that stimulates bone cell proliferation and bone matrix formation in vitro. We have postulated that this factor could be involved in the coupling mechanism. Subsequently, a similar factor which stimulates bone cell proliferation, collagen synthesis and bone formation in vitro was extracted from embryonic and adult bones. The factor partially purified from human bone, designated as human skeletal growth factor, has molecular weight, heat sensitivity and biological activity similar to the factor found in bone conditioned medium. Many other biologically active factors have also been extracted from bone cells or demineralized bone by different laboratories. Their actions on bone cells range from chemotactic to mitogenic. These recently discovered bone factors emphasize that there is important regulation of bone metabolism at the local level.

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Human skeletal growth factor: characterization of the mitogenic effect on bone cells in vitro

Cited by 49 publications

References 14 publications

The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone

The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone

Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats.

Bone-derived factors active on bone cells

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