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In recent years, significant progress has been made on the research of Bone Morphogenetic Protein-7, BMP-7 (OP-1). BMP-7 is a growth- and differentiating-factor and a member of the TGF-β or Transforming Growth Factor-beta Superfamily. Ever since recombinantly produced human BMP-7 (rhBMP-7) became available in the early 1990s research in this area intensified. Many publications and presentations were issued detailing the ability of rhBMP-7 to induce new bone formation and to investigate this as an option to solve a wide variety of orthopedic problems.

BMP-7's activity in bone regeneration has been established through numerous animal trials. Work has been presented on the potency of rhBMP-7 in joint revision arthroplasty, fracture healing and spinal fusion. rhBMP-7 has been investigated in a prospective controled human trial as an alternative for autograft in the treatment of tibial non-unions. In the not too distant future surgeons may have a new tool available in their daily practice for stimulating regeneration of bone and other skeletal tissue, though still many question on issues like dosing, predictability of outcomes, suitable indications and surgical techniques remain yet unanswered.

An extractable bone-inducing agent has recently been identified in freeze-dried preparations of Saos-2 cultured human osteosarcoma cells. Although not all osteoinductive components of Saos-2 cell extracts have been identified, we have shown that Saos-2 cells express high levels of mRNA for bone morphogenetic proteins (BMPs)-1,2,3,4 and 6. Any or all of these BMPs (plus possible unknown factors) may be involved in ectopic bone induction, and may act as paracrine agents, conveying morphogenetic information to juxtaposed osteoprogenitor cells. Our objectives in this study were: 1) to determine whether Saos-2 cells secrete BIA into their culture medium; and 2) if secreted, to determine whether released bone-inducing agent is soluble and/or particulate and contains BMPs. Saos-2 cells were grown to confluence, and then overlaid with serum-free DMEM culture medium for 48 hours. The serum-free conditioned medium was then decanted and filtered through 0.45μ pore-size filters to retain any vesicles or other particulates released by the cells. Particulate protein retained on the 0.45μ filter (designated "retentate") was extracted into 6M urea and bioassayed for bone-inducing activity in Nu/Nu mice, along with soluble media protein that had passed through the 0.45μ filter (designated "filtrate") plus freeze-dried Saos-2 cells from which conditioned the culture medium was obtained. Results indicate that the bone-inducing agent of Saos-2 cells is not only retained by the cells, but is also secreted in both soluble and particulate forms into serum-free conditioned medium. Bone-inducing activity (per mg protein) is more concentrated in the particulate fraction, which is shown by electron microscopy to contain a mixture of vesicles (similar to matrix vesicles) plus electron dense granules (resembling ribosomes) and 10 mM microfilaments (of possible collagenous or cytoskeletal origin). BMP-1,2,3,4,6 and 7 were detected by western blots in both the soluble and particulate fractions of conditioned medium. Thus, it is indicated that Saos-2 cells secrete an osteoinductive factor which may function in vivo as a paracrine morphogenetic agent.

Jaw bone, such as alveolar bone for tooth socket, has many characteristics and remodeling mechanisms dissimilar to the other bony tissues. This study aimed to clarify the healing mechanism and process of jaw bone formation in the case of mandible bone defect in dog using porous hydroxyapatite-BMP composite. 70% porosity and 100-200 micron meter pore sized HAP and BMP composite was implanted into artificially scooped out mandible bones of dog. After one week, the HAP-BMP composite accelerated osteoblast differentiation and osteoid formation in contrast to the BMP implant experiments that showed no bone formation. Around HAP-BMP composite, immature bone formed after one week and definite fibrous bone formation was observed after three weeks. It was observed that after one week fibrous tissue surrounded the HAP-BMP composite and there was little or no direct evidence of osteoconduction from the surrounding bone. After five weeks, newly formed bone was substituted by mature bone with remodeling similar to healing process. After remodeling process started osteoconduction was clearly observed. The results suggested that in dog jaw bones HAP-BMP composite introduced mesenchymal cells differentiation at the early stage and influenced to activate these cells and bone formation.

Concave defects in bone after tooth extraction often cause various difficulties in prosthetic dentistry, which require an effective method of local bone recovery. We have devised porous particles of hydroxyapatite (PPHAP) for bone augmentation. Recombinant human BMP2 was combined with PPHAP and implanted into the sockets after extraction of premolars in rabbit mandibles. Control groups with PPHAP alone, and without any implant were designed. Quantitative histological analysis of bone formation was done in the divided areas within the socket, the orifice, middle, and, bottom areas in the apical direction, and also in the central and lateral wall areas in the horizontal direction. Four weeks after operation, in the non implant and the PPHAP-alone groups, active bone formation was limited to the bottom and lateral wall areas. Little bone formation was observed in the central and orifice areas. On the other hand, in the BMP2/PPHAP group new bone formation was seen as early as in 2 weeks in almost all areas of the socket. After 4 weeks, total amounts of new bone in the BMP2/PPHAP group were about two times higher than in the control. The bone formation was particularly rich in the orifice areas, resulting in the flat or convex-shaped recovery of alveolar bone after tooth extraction. This application of the rhBMP2/PPHAP composite material will provide a useful tool in clinical dentistry.