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PubMed1996

Basic fibroblast growth factor for stimulation of bone formation in osteoinductive or conductive implants.

Basic Fibroblast Growth Factor (bFGF) is one of the endogenous factors found in bone matrix. bFGF is a mitogen for many cell types, including osteoblasts and chondrocytes. It can stimulate angiogenesis and osteoblast gene expression. The purpose of this study was to investigate whether exogenous bFGF can stimulate the formation of bone in bone grafts and in a bone graft substitute. In a model using demineralized bone matrix implants for bone induction, a dose of 15 ng bFGF per implant increased the number of chondrocytes and the amount of bone, whereas 1900 ng greatly inhibited cartilage and bone formation. These results are consistent with previous studies with this model, showing that a lower dose of bFGF increased bone calcium content and a higher dose reduced it. Thus, exogenous bFGF can stimulate proliferation during early phases of bone induction. A new device, the bone conduction chamber, was developed for the application of bFGF to bone conductive materials. This model made it possible to demonstrate a difference between the conductive properties of bone grafts and porous hydroxyapatite. bFGF increased bone ingrowth into bone graft inside the chamber and showed a biphasic dose-response curve, so that 8-200 ng per implant (0.4-10 ng/mm3) increased bone ingrowth, but higher or lower doses had no effect. The same doses had the same effects in porous hydroxyapatite. In both bone grafts and porous hydroxyapatite, the highest dose still caused an increase in ingrowth of fibrous tissue. The effect on bone ingrowth was first detected after 6 weeks, regardless if administration of bFGF started at implantation or 2 weeks later, using an implanted minipump. Hyaluronate gel was effective as a slow-release carrier for bFGF. In conclusion, bFGF stimulates bone formation in bone implants, depending on dose and method for administration.

Animals↗
PubMed1990

[Ultrastructural study of bone cells and matrix incident in experimental periodontitis].

The purpose of this study was to examine the process of bone destruction and also to examine the ultrastructural features of the cells and the resorbed sites of bone matrix in experimental periodontitis. To induce the periodontitis, a defect was prepared with a endodontic reamer in the proximal surfaces of the upper 1st and 2nd molars of rats. The process of the bone resorption was examined histopathologically once a week for 3 weeks. Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were used to examine the cells and the bone matrix using the specimens taken 2 or 3 weeks after the start of the experiment. The alveolar bone resorptions of interdental areas were observed 2 weeks after starting the experiment and it continued to progress longitudinally. After 3 weeks, concave bone loss appeared on the buccal surfaces of the bone. The resorbed bone surface revealed by TEM typical osteoclasts, macrophages and mononuclear cells resorbing collagen fibrils. These cells resorbing collagen fibrils which worked with the osteoclasts appeared frequently in resorbed sites. Numerous osteoblasts appeared on the resorbed area. However, judging from their undeveloped organelles, their function seemed to remain inactive and unproductive. SEM showed many resorbed lacunae in the alveolar bone in interdental areas and the differences in the ultrastructural features of the resorption lacunae were distinctive. These findings suggest that the massive and rapid bone resorption in experimental periodontitis is the result of increased osteoclastic activity and depressed osteoblastic activity. The different ultrastructural features of each lacunae were results of the resorbing stage.

Alveolar Bone Loss↗
PubMed1993

Biological evaluation of an ionomeric bone cement by osteoblast cell culture methods.

Periosteal derived bovine osteoblast-like cells migrated in culture onto an ionomeric cement. Cell cultures were maintained for 4 weeks and used to study the in vitro behaviour of cells on the ionomeric bone cement (IC). The cells produced bone matrix proteins (osteocalcin, bone sialoprotein II) and were osteoblast-like. The osteoblast-like cells colonized the substrate in monolayers and produced an extracellular matrix as seen by light and scanning electron microscopy. Morphological comparison between cells growing on the ionomeric bone cement and cortical bone revealed no significant difference in phenotypic expression. Staining for aluminium in osteoblasts growing on the IC showed an uptake and storage of aluminium in the cells. Energy dispersive X-ray microanalysis revealed high concentrations of aluminium and silicon in the periosteal tissue. Despite the known toxic effect of aluminium in vivo and in vitro on osteoblasts, no signs of toxicity were apparent on light and scanning electron microscopy analysis.

Aluminum Oxide↗
PubMed1992

Interleukin-1 stimulates release of insulin-like growth factor-I from neonatal mouse calvaria by a prostaglandin synthesis-dependent mechanism.

Interleukin-1 alpha (IL-1 alpha) and IL-1 beta are cytokines produced by cells of the immune system and nonimmune cells, such as osteoblasts. IL-1 alpha and IL-1 beta have potent stimulatory effects on bone resorption and also have mixed effects on bone formation, suggesting that they play an important role in local regulation of bone turnover. The present study examined paracrine mechanisms underlying effects of IL-1 on bone formation. Bone formation is regulated at the local level by polypeptide growth factors such as insulin-like growth factor-I (IGF-I). IGF-I is a relatively abundant growth factor in bone matrix, is produced by osteoblasts, and stimulates osteoblastic cell proliferation and bone matrix synthesis. Recent evidence suggests that IGF-I also stimulates osteoclast formation and bone resorption. To determine whether increased or decreased IGF-I production in bone might mediate some of the effects of IL-1 on bone turnover, the effects of IL-1 alpha and IL-1 beta on IGF-I release from neonatal mouse calvaria in organ culture were examined. IL-1 alpha and IL-1 beta stimulated resorption and increased the release of IGF-I into the medium during 6 days of culture. Maximal stimulation of resorption occurred at lower concentrations of IL-1 alpha and IL-1 beta (1 pM) than were required for maximum stimulation of IGF-I release (10 pM). IL-1 beta also increased steady state levels of 7.5- and 0.9-kilobase IGF-I mRNA transcripts in total RNA extracted from cultured calvaria at 24 h. The cyclooxygenase inhibitor indomethacin (1 microM) inhibited IL-1 beta-induced prostaglandin E2 (PGE2) production and inhibited resorption and release of IGF-I from calvaria. Indomethacin had a smaller effect on PTH-induced IGF-I release and had no significant effect on PTH-induced resorption. These results suggest that the effects of IL-1 on resorption and release of IGF-I may be mediated in part by a prostaglandin-dependent mechanism. Consistent with this hypothesis, PGE1 and PGE2 stimulated resorption and release of IGF-I. The dose responses for PGE2 stimulation of resorption and stimulation of IGF-I release were equivalent. The results are consistent with the hypotheses that 1) IL-1 stimulates IGF-I production by bone cells, in part by PG-dependent mechanisms; 2) the effects of IL-1 and PGs on bone formation and resorption may be mediated by locally induced secretion of IGF-I and other growth factors in bone.

Animals↗
PubMed2003

Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities.

The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations of specific collagen fragments believed to discriminate between cathepsin K and MMP cleavage. Next, we provide evidence that MMPs are very critical for osteoclast migration, thereby controlling also the cell-matrix interactions required for cell attachment/detachment. The evidence supporting this role is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we emphasize the many distinct ways MMPs may alter focally the extracellular environment thereby regulating the osteoclast behavior. Although the understanding of MMPs in osteoclast biology is rapidly expanding, it is suspected that important roles remain to be discovered.

Animals↗
PubMed1990

Phosphorylation of extracellular bone and dentine matrix proteins.

Phosphoproteins appear to be involved in several ways in the regulation of the orderly deposition and crystal growth of mineral within the performed collagenous matrix of bone and dentine. The phosphorylation of these proteins is not yet understood. Potential protein kinases were extracted from an osteoblast-like cell line, ROS 17/2.8. The ROS 17/2.8 line was shown to produce a full complement of known kinases. However, neither bone phosphoproteins (BPP) nor dentine phosphophoryn (DPP) could be phosphorylated by the messenger dependent kinases. DPP and dephosphorylated BPP (dBPP) were substrates for a unique messenger independent kinase distinct from casein kinase II, and dDPP was a still better substrate. Thus, BPP and DPP are phosphorylated by a unique kinase or set of kinases which are messenger independent and have very specific substrate sequence requirements.

Bone and Bones↗
PubMed1984

A fraction from extracts of demineralized adult bone stimulates the conversion of mesenchymal cells into chondrocytes.

Demineralized adult bone contains factors which stimulate nonskeletal mesenchymal cells to undergo a developmental progression resulting in de novo endochondral ossification. In this study, isolated embryonic stage 24 chick limb bud mesenchymal cells maintained in culture were utilized as an in vitro assay system for detection of specific bioactive components solubilized from adult chicken bone matrix. Guanidinium chloride extracts (4 M) of demineralized-defatted bone were fractionated and tested in limb mesenchymal cell cultures for possible effects upon growth and chondrogenesis. Two low-molecular-weight fractions were found to be active in these cultures. A cold water-insoluble, but warm Tris-buffered saline-soluble fraction provoked a dose-dependent increase in the amount of cartilage formed after 7 days of continuous exposure as evidenced by an increased number of chondrocytes observed in living cultures, elevated cell-layer-associated 35S incorporation per microgram DNA, and greater numbers of toluidine blue-staining foci (i.e., cartilage nodules). Growth inhibitory substances were detected in a low-molecular-weight, water-soluble fraction; 7 days of continuous exposure to this material resulted in less cartilage formation and reduced cell numbers (accumulated DNA) on each plate. These observations demonstrate the usefulness of stage 24 chick limb bud cell cultures for identifying bioactive factors extracted from adult bone matrix. In addition, the action of these factors on mesenchymal cells may now be studied in a cell culture system.

Animals↗
PubMed1999

Osteoblast-derived acetylcholinesterase: a novel mediator of cell-matrix interactions in bone?

The adhesive interactions that occur between bone cells and the developing matrix during bone formation help guide coupled remodeling and the maintenance of bone mass. Here, we provide evidence that acetylcholinesterase (AChE) is a novel osteoblast-derived mediator of cell-matrix interactions in bone. These findings complement an increasing body of evidence which suggests that AChE, in addition to its role in terminating cholinergic signaling, may be instrumental in regulating cellular differentiation and adhesion. We have shown, using RT-PCR, that osteosarcoma cell lines and primary cultures of osteoblasts express AChE mRNA. Expression appeared to be differentiation-dependent, and restricted to AChE splice variants containing the T subunit (exon 6). Immunofluorescent localization demonstrated that these osteoblastic cells expressed protein for AChE with an intracellular vesicular distribution. Immunohistochemistry on tissue sections confirmed AChE expression by osteoblasts in vivo, and revealed the presence of AChE along cement lines, also identified by enzyme histochemistry. In vitro functional studies indicated that osteoblast-like cells adhered specifically to and spread on AChE substrates, but did not interact with butyrylcholinesterase, a closely related protein. Our evidence strongly implicates AChE as a novel bone matrix protein, capable of mediating cell-matrix interactions, and as such may be a principal participant in organized bone formation and the regulation of remodeling.

Acetylcholinesterase↗
PubMed1997

Multinucleated giant cells recruited by implantation of octacalcium phosphate (OCP) in rat bone marrow share ultrastructural characteristics with osteoclasts.

The ultrastructural characteristics of multinucleated giant cells (MNGCs) on octacalcium phosphate (OCP) and hydroxyapatite (HA) were investigated in comparison with those of osteoclasts, when the synthetic OCP and HA were implanted in rat bone marrow. The morphological difference in the MNGCs were shown between OCP and HA implants in 2 weeks after implantation. The MNGC on the implanted OCP (i-OCP) developed the ruffled border-like structure and the clear zone-like structure. The i-OCP was frayed where it was in contact with the ruffled border-like structure. The MNGC on the implanted HA (i-HA) developed the clear zone-like structure, whereas no ruffled border was seen. The surface of i-HA associated with the MNGC was smooth and not frayed. Bone formed directly on the OCP or HA implants. The interface between the i-OCP and bone matrix interdigitated, whereas that between the i-HA and bone matrix was comparatively smooth. The present study suggested that the i-OCP could be resorbed by the MNGCs which share some ultrastructural characteristics with osteoclasts.

Animals↗
PubMed2006

Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1).

We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial-mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-beta family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions.

Animals↗
PubMed2001

A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice.

Bone resorption is a dominant feature of many bone metastases and releases factors from the bone matrix that can promote the expression of the metastatic phenotype in cancer cells. Since proteolytic enzymes, including matrix metalloproteinases (MMPs) contribute to bone destruction by metastatic tumour cells and host cells, we have examined the effect of a MMP inhibitor, batimastat, on the ability of MDA-MB-231 cells to degrade bone in vitro and to form bone metastases in BalbC nu/nu mice. In vitro, the neoplastic cells produced MMP-2 and MMP-9, degraded [3H]-proline-labelled osteoblast matrices, and formed resorption pits in cortical bone. These phenomena were inhibited by < or = 20 microM batimastat. To induce vertebral and long bone metastases in vivo, 1x10(5) MDA-MB-231 cells were injected into the arterial circulation of BalbC nu/nu mice. Test groups were also given 30 mg/kg batimastat intraperitoneally (i.p.). After 21 days, the long bone metastases were characterised by a 67% reduction of metaphyseal medullary bone and complete replacement of marrow by tumour. In tumour-bearing mice that had been treated with 30 mg/kg batimastat i.p., the tumour volume decreased 8-fold, osteolysis was inhibited by 35%, and replacement of the bone marrow by tumour was inhibited by 65%. Similar effects were observed in the vertebral metastases. These data provide evidence that MDA-MB-231 cells can degrade osteoblast matrices and mineralised bone in vitro and support the hypothesis that MMPs are involved in the pathogenesis of osteolytic bone metastases in vivo. They demonstrate that an agent which inhibits proteolysis can retard the development of osteolytic bone metastases in this model.

Animals↗
PubMed1987

Bone structure and function.

Bone is a complex, living, constantly changing tissue. The architecture and composition of cancellous and cortical bone allow the skeleton to perform its essential mechanical functions. The stiffer cortical bone responds more slowly to changes in loads while cancellous bone has a much larger surface area per unit volume and a greater rate of metabolic activity. Periosteum covers the external surface of bone and consists of two layers: an outer fibrous layer and an inner more cellular and vascular layer. The inner osteogenic layer or cambium layer can form new bone while the outer layer forms part of the insertions of tendons, ligaments and muscles. The cortical bone of diaphyses and metaphyses has a dual blood supply that allows loss of one source of circulation without adversely affecting the viability of the tissue. Many epiphyses, even in adults, depend only on a single source of blood supply, the penetrating epiphyseal vessels. For this reason epiphyseal bone may infarct more easily than metaphyseal or diaphyseal bone. The bone matrix has an organic component, primarily type I collagen, which gives it tensile strength and an inorganic component, primarily hydroxyapatite, which gives it stiffness to compression. Specialized populations of bone cells form, maintain and remodel this matrix. We recognize four types of bone cells based on their locations, morphology and functions: osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts. Osteoblasts develop from undifferentiated cells while osteocytes form from osteoblasts. Osteoclasts have a separate stem cell line, blood-borne monocytes. Bone matrix apparently attracts these monocytes and stimulates their differentiation into osteoclasts. The processes of bone modeling and remodeling require osteoclastic resorption of bone matrix and deposition of a new matrix by osteoblasts. Modeling shapes and reshapes bones during growth and stops at skeletal maturity. Physiologic remodeling does not change bone shape and consists of bone resorption followed by bone deposition in approximately the same location. Since it continues throughout life it appears to be important for maintenance of the skeleton, but its exact function remains obscure. Adaptive remodeling is the response of the bone to altered loads and may alter the strength, density and shape of bone. In recent years understanding of the control of bone cell function has increased significantly. The study of electrical effects on bone formation has lead to new treatments of nonunions and delayed unions. Physicians have applied understanding of matrix-induced bone formation to reconstruction of skeletal defects.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Development↗
PubMed1988

Immunohistochemical localization of osteonectin in developing human and calf bone using monoclonal antibodies.

Osteonectin was immunolocalized in human fetal and calf neonatal developing bone using newly developed monoclonal antibodies. The protein was localized to the cytoplasm of osteoblasts and young osteocytes. In bone matrix, strong reactivity was found in newly laid down osteoid. Bone matrix immunoreactivity was enhanced by pretreatment of sections with proteases, possibly because of an unmasking of epitopes engaged in protein-protein interactions. Osteonectin immunoreactivity was also found in preosteoblasts in all types of human fetal osteogenesis (membranous, endochondral, subperiosteal, and mantellar (Meckel's cartilage) ossification), and in some chondrocytes of metaphyseal growth plate, possibly modulating towards an osteoblastic phenotype.

Alkaline Phosphatase↗
PubMed1997

Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures.

We have shown earlier that mechanical stimulation by intermittent hydrostatic compression (IHC) promotes alkaline phosphatase and procollagen type I gene expression in calvarial bone cells. The bone matrix glycoprotein osteopontin (OPN) is considered to be important in bone matrix metabolism and cell-matrix interactions, but its role is unknown. Here we examined the effects of IHC (13 kPa) on OPN mRNA expression and synthesis in primary calvarial cell cultures and the osteoblast-like cell line MC3T3-E1. OPN mRNA expression declined during control culture of primary calvarial cells, but not MC3T3-E1 cells. IHC upregulated OPN mRNA expression in late released osteoblastic cell cultures, but not in early released osteoprogenitor-like cells. Also, in both proliferating and differentiating MC3T3-E1 cells, OPN mRNA expression and synthesis were enhanced by IHC, differentiating cells being more responsive than proliferating cells. These results suggest a role for OPN in the reaction of bone cells to mechanical stimuli. The severe loss of OPN expression in primary bone cells cultured without mechanical stimulation suggests that disuse conditions down-regulate the differentiated osteoblastic phenotype.

3T3 Cells↗
PubMed1998

Role of morphogenetic proteins in skeletal tissue engineering and regeneration.

Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleaned through studies on inductive signals, responding stem cells, and the extracellular matrix to design and construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is a prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints.

Animals↗
PubMed2006

A chondroitin sulfate chain attached to the bone dentin matrix protein 1 NH2-terminal fragment.

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein shown by gene ablations to be critical for the proper mineralization of bone and dentin. In the extracellular matrix of these tissues DMP1 is present as fragments representing the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) portions of the cDNA-deduced amino acid sequence. During our separation of bone noncollagenous proteins, we observed a high molecular weight, DMP1-related component (designated DMP1-PG). We purified DMP1-PG with a monoclonal anti-DMP1 antibody affinity column. Amino acid analysis and Edman degradation of tryptic peptides proved that the core protein for DMP1-PG is the 37-kDa fragment of DMP1. Chondroitinase treatments demonstrated that the slower migration rate of DMP1-PG is due to the presence of glycosaminoglycan. Quantitative disaccharide analysis indicated that the glycosaminoglycan is made predominantly of chondroitin 4-sulfate. Further analysis on tryptic peptides led us to conclude that a single glycosaminoglycan chain is linked to the core protein via Ser74, located in the Ser74-Gly75 dipeptide, an amino acid sequence specific for the attachment of glycosaminoglycans. Our findings show that in addition to its existence as a phosphoprotein, the NH2-terminal fragment from DMP1 occurs as a proteoglycan. Amino acid sequence alignment analysis showed that the Ser74-Gly75 dipeptide and its flanking regions are highly conserved among a wide range of species from caiman to the Homo sapiens, indicating that this glycosaminoglycan attachment domain has survived an extremely long period of evolution pressure, suggesting that the glycosaminoglycan may be critical for the basic biological functions of DMP1.

Amino Acid Sequence↗
PubMed1993

Expression of insulin-like growth factors during bone induction in rat.

Bone formation was studied after intramuscular implantation of demineralized bone matrix. Ash weight determinations were used to verify the bone-forming ability of implants, and confirmed that no bone was formed when nonactive implants (stripped of their bone-forming ability) were used. A solution hybridization/RNase protection assay was used for the detection of specific mRNA transcripts in the implants and surrounding tissue. Analysis of insulin-like growth factor I (IGF-I) mRNA showed a transient increase peaking on day 3 following implantation. Radioimmunoassay (RIA) for IGF-I-like immunoreactivity indicated a corresponding increase of IGF-I peptide in extracts from the implants at that time point. IGF-II mRNA and alkaline phosphatase mRNA reached highest levels around day 11 following implantation. Bone formation in old rats, 50 weeks of age, was associated with lower IGF-I mRNA levels 3 days after implantation compared with young animals. IGF-II mRNA levels were also affected and tended to be higher 12 days after implantation compared with young animals. These results indicate that IGFs could be paracrine or autocrine factors in the bone-forming process. During this process, IGF-I mRNA is expressed at an early stage, in correlation with the recruitment and proliferation of surrounding mesenchymal cells, whereas IGF-II mRNA is activated significantly later, correlating to the beginning of the actual calcifying process during endochondral bone formation.

Aging↗
PubMed1993

Insulinlike growth factor gene expression in human fracture callus.

The effects of insulinlike growth factors on bone and cartilage-derived cells in culture have been extensively investigated, but there is little information on their role in vivo in bone, especially in fracture healing. This study investigated insulinlike growth factor (IGF) I and II mRNA expression in normally healing human fractures by in situ hybridization. Endothelial and mesenchymal cells at the granulation tissue stage expressed IGF-II mRNA. At the stage of bone and cartilage formation, osteoblasts and non-hypertrophic chondrocytes expressed mRNA for both IGF-I and II. Some osteoclasts were positive for IGF-II mRNA at the stage of bone remodeling. The greater time span of IGF-II expression relative to IGF-I reflects the predominance of IGF-II in human bone matrix. Taken together with the known effects of IGFs on bone and cartilage cells in vitro, these findings support a role for IGFs in local cellular regulation in human fracture healing.

Adolescent↗