This study was designed to test the hypothesis that increased physical contact, experimentally induced, would promote greater maternal responsiveness and more secure attachment between infant and mother. Low-SES mothers of newborn infants were randomly assigned to an experimental group (n = 23) that received soft baby carriers (more physical contact) or to a control group (n = 26) that received infants seats (less contact). Using a transitional probability analysis of a play session at 31/2 months, it was demonstrated that mothers in the experimental group were more contingently responsive than control mothers to their infants' vocalizations. When the infants were 13 months old, the Ainsworth Strange Situation was administered. Significantly more experimental than control infants were securely attached to their mothers. We infer from these results that for low-income, inner-city mothers, there may be a causal relation between increased physical contact, achieved through early carrying in a soft baby carrier, and subsequent security of attachment between infant and mother.

Subcutaneous implantation of deminerli bone matrix initiates a sequence of developmental events, which nate in endochondial bone formation. During early stages of development of matrix-induced Impts, ED1, Tapositive monocytes-macrophages were observed, sgeting that in the initial phases of the endochondral bone formation de, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression ofBMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissocition constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type hi transforming growth factor (TGF-l1) in human monocytes. TGF-p1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-3 are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-fl1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.Bone has considerable potential for repair and regeneration, and the stages of fracture repair recapitulate the sequential developmental stages of embryonic endochondral bone formation. A cellular cascade that mimics embryonic endochondral bone development can be induced locally by implantation of demineralized bone matrix in extraskeletal sites (1-3). The cellular and biochemical events of this matrix-induced endochondral bone-forming cascade have been well characterized (3). Upon implantation of demineralized bone matrix, there is a transient immigration of polymorphonuclear leukocytes on day 1. This is followed by migration and attachment of mesenchymal cells to the matrix by day 3. These mesenchymal progenitor cells proliferate and differentiate into chondroblasts and chondrocytes on days 6-7. Vascularization of the implant occurs concomitantly with calcification of the hypertrophic cartilage matrix on day 9, and the cartilage is resorbed and replaced by new bone on days 10-12. Bone remodeling (days 12-18) and differentiation of hematopoietic cells result in formation of an ossicle complete with all associated marrow elements by day 21.Although the precise molecular mechanisms involved in this biological cascade a...

The human osteoinductive proteins BMP-2a and BMP-2b have been cloned and expressed in mammalian cells. In order to improve expression levels we examined the role of the proregion in assembly and export. Use of the BMP-2a proregion combined with the mature region of BMP-2b leads to dramatically improved expression of mature BMP-2b. Mature BMP-2b has been purified to near homogeneity from the BMP-2a/2b hybrid, and its structural properties and biological activity determined. Recombinant mature BMP-2b homodimer elicits bone formation in vivo.

We have identified a new member of the transforming growth factor-beta (TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is highly related to bone morphogenetic protein-3 (BMP-3). The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. In the mature carboxy-terminal domain GDF-10 is more homologous to BMP-3 (83% amino acid sequence identity) than to any other previously identified TGF-beta family member. GDF-10 also shows significant homology to BMP-3 (approximately 30% amino acid sequence identity) in the pro- region of the molecule. Based on these sequence comparisons, GDF-10 and BMP-3 define a new subgroup within the larger TGF-beta superfamily. By Northern analysis, GDF-10 mRNA was detected primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect.

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The presence of growth and differentiation factors in bone has been demonstrated by subcutaneous implantation of demineralized bone matrix that initiates new cartilage and bone morphogenesis. The genes for bone morphogenetic proteins (BMPs) have been cloned and expressed. Recombinant BMPs induce endochondral bone formation in vivo. The multistep sequential developmental cascade consists of chemotaxis, mitosis, and differentiation of cartilage and bone. The pleiotropic response has been well characterized. BMPs stimulate osteogenic and chondrogenic phenotypes. Natural bovine osteogenin (BMP-3) and recombinant BMP-4 are equipotent in chemotaxis, limb bud chondrogenesis, cartilage maintenance, and in vivo bone induction. There are multiple isoforms of BMPs, raising the biologic relevance of the redundancy. The mode of action and second messengers are not clear. BMPs appear to have cognate receptors as demonstrated by iodinated BMP-2B (BMP-4). Other novel members of the BMP family include osteogenic protein 1 (BMP-7) and osteogenic protein 2 (BMP-8). Bone morphogenetic proteins are members of the transforming growth factor-beta superfamily and include three distinct subfamilies: BMP-2, BMP-3, and BMP-7. Native BMP-3 and recombinant BMP-4 bind type IV collagen of the basement membrane. This novel connection may be the long elusive mechanistic explanation for the requirement of angiogenesis and vascular invasion for bone morphogenesis. BMPs may have a role in fracture repair, periodontal regeneration, and alveolar ridge augmentation.

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