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A H Reddi

Publications and source records attributed to A H Reddi.

At least 19 recordsLinked to original sources
PubMed2006

Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.

OBJECTIVE: Microfracture is used to treat articular cartilage injuries, but leads to the formation of fibrocartilage rather than native hyaline articular cartilage. Since bone morphogenetic protein 7 (BMP-7) induces cartilage differentiation, we hypothesized that the addition of the morphogen would improve the repair tissue generated by microfracture. We determined the effects of these two treatments alone and in combination on the quality and quantity of repair tissue formed in a model of full-thickness articular cartilage injury in adolescent rabbits. DESIGN: Full-thickness defects were made in the articular cartilage of the patellar grooves of forty, 15-week-old rabbits. Eight animals were then assigned to (1) no further treatment (control), (2) microfracture, (3) BMP-7, (4) microfracture with BMP-7 in a collagen sponge (combination treatment), and (5) microfracture with a collagen sponge. Animals were sacrificed after 24 weeks at 39 weeks of age. The extent of healing was quantitated by determining the thickness and the surface area of the repair tissue. The quality of the repair tissue was determined by grading specimens using the International Cartilage Repair Society Visual Histological Assessment Scale. RESULTS: Compared to controls, BMP-7 alone increased the amount of repair tissue without affecting the quality of repair tissue. Microfracture improved both the quantity and surface smoothness of repair tissue. Compared to either single treatment, the combination of microfracture and BMP-7 increased both the quality and quantity of repair tissue. CONCLUSIONS: Microfracture and BMP-7 act synergistically to stimulate cartilage repair, leading to larger amounts of repair tissue that more closely resembles native hyaline articular cartilage.

Animals↗
PubMed2003

Interleukin-17 family and IL-17 receptors.

Interleukin-17 (IL-17) is a pro-inflammatory cytokine secreted by activated T-cells. Recently discovered related molecules are forming a family of cytokines, the IL-17 family. The prototype member of the family has been designated IL-17A. Due to recent advances in the human genome sequencing and proteomics five additional members have been identified and cloned: IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. However, the ligand specificities of many of these receptors have not been established. The IL-17 signaling system is operative in disparate tissues such as articular cartilage, bone, meniscus, brain, hematopoietic tissue, kidney, lung, skin and intestine. Thus, the evolving IL-17 family of ligands and receptors may play an important role in the homeostasis of tissues in health and disease beyond the immune system. This survey reviews the biological actions of IL-17 signaling in cancers, musculoskeletal tissues, the immune system and other tissues.

Amino Acid Sequence↗
PubMed2003

Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration.

BACKGROUND: Articular cartilage homoeostasis is critical for joint function. The steady state homoeostasis of articular cartilage is a balance between anabolic morphogens such as cartilage derived morphogenetic proteins (CDMPs) and bone morphogenetic proteins (BMPs) of the BMP family and catabolic cytokines such as interleukin (IL)1, IL17, and tumour necrosis factor alpha. Although bone and articular cartilage are adjacent tissues, there is a profound difference in their regeneration potential. Bone has the highest potential for regeneration. On the other hand, articular cartilage is recalcitrant to repair. OBJECTIVE: To examine the hypothesis that the feeble innate regeneration ability of cartilage is due to the preponderance of catabolic cytokines such as IL1 and IL17. RESULTS: During a systematic investigation of CDMPs and cytokines IL17B (chondroleukin) was found in bovine articular cartilage. DISCUSSION AND CONCLUSIONS: BMP-7 and IL17B are present in articular cartilage and synthesised in chondrocytes as shown by northern blots and real-time reverse transcription-polymerase chain reaction. The coexistence of anabolic morphogens and catabolic cytokines in articular cartilage has important implications for cartilage homoeostasis and regeneration. The networks of signalling systems of morphogens and cytokines determine the net capacity for regenerative morphogenesis of articular cartilage. Finally, the feeble innate capacity for articular cartilage may be improved by targeted therapy by soluble receptors to block catabolic cytokines.

Animals↗
PubMed2002

Bone morphogenetic protein-7 selectively enhances mechanically induced bone formation.

The responses of bone cells to skeletal loading are clearly an important factor in bone biology, but much remains to be learned about the role of these responses in skeletal development, maintenance, and tissue repair. Bone morphogenetic proteins (BMPs) are key regulators of bone formation. We examined the effect of BMP-7 on periosteal and endosteal bone formation in response to increased mechanical loading using the rat tibial bending model. Female Sprague-Dawley rats were divided into four groups of six rats each. Three groups received four point bending loading at 60 N force; the fourth group received sham loading at the same force. The right tibia received 36 cycles of loading on Monday, Wednesday, and Friday for 2 weeks; the left tibia served as a nonloaded control. Just prior to loading, the three loaded groups were injected intraperitoneally with vehicle only or 10 microg/kg or 100 microg/kg of recombinant human BMP-7. Half the sham group received vehicle, and half were given 100 microg/kg of BMP-7. Bone forming surfaces were labeled twice in vivo with calcein, and histomorphometry was performed to quantify periosteal and endosteal bone formation in the loaded and control tibiae. BMP-7 had no effect on periosteal or endosteal bone formation in control or sham-loaded tibiae. Loading produced significantly more woven bone on the periosteal surface than sham loading, but BMP-7 treatment had no effect on this response. Endosteal bone formation was entirely lamellar, and loading (but not sham loading) increased the endosteal mineral apposition and bone formation rates. The higher BMP-7 dose more than doubled the load-induced increase in endosteal lamellar bone formation rate, primarily by increasing the amount of bone forming surface.

Animals↗
PubMed2002

The temporal sequence of spontaneous repair of osteochondral defects in the knees of rabbits is dependent on the geometry of the defect.

Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect. Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect. The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm.

Animals↗
PubMed2000

Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN.

This commentary is a concise discussion of the interactions between bone morphogenetic proteins (BMPs) and their binding proteins in bone and cartilage morphogenesis. BMPs are a family of growth and differentiation factors, and they act on mesenchymal cells to induce cartilage and bone differentiation in concentration-dependent thresholds. The BMP-BMP receptor binding leads to a cascade of signaling and transcription of BMP response genes. BMP binding proteins, noggin, chordin and DAN, act as antagonists and determine the bioavailability of BMPs for binding to cognate receptors to elicit the biological response. Noggin null mice with unrestricted action of BMPs exhibit defects in joint morphogenesis. BMPs and their binding proteins may reciprocally regulate the dynamic topography of joints, muscle, tendons and ligaments during morphogenesis of the skeleton. In addition, BMP actions may be potentiated by twisted gastrulation. BMPs and their binding proteins may play a critical role in regeneration of cartilage in osteoarthritis.

Animals↗
PubMed2000

Bone morphogenetic proteins and skeletal development: the kidney-bone connection.

The bone morphogenetic proteins (BMPs) are a family of pleiotropic morphogens isolated and cloned from the demineralized extracellular matrix of bone. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote and maintain bone and cartilage. The pleiotropic effects of BMPs are based on concentration-dependent thresholds. Targeted disruption of gene action by homologous recombination has demonstrated the role of BMP 7 in kidney, eye and skeletal development. BMP 7 is critical for kidney tubulogenesis, retinal pigmented epithelium differentiation and skeletal pattern. BMP 7 is also synthesized by the kidney and is detectable in serum; hence BMP 7 is both an autocrine and endocrine morphogen. It is likely renal BMP 7 may influence skeletal development and growth in children although there may be sources of other BMPs with skeletogenic actions. In conclusion, we are beginning to unravel the mysteries of kidney-bone connection with special reference to pediatric nephrology.

Animals↗
PubMed2000

Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials.

Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of many structures and asymmetry of some, culminating in the adult form. Tissue engineering is the emerging discipline of design and construction of spare parts for the human body to restore function based on principles of molecular developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are inductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regeneration and is a prototype model for tissue engineering based on morphogenesis. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and permitted the isolation of bone morphogens. Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conductive strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consisting of extracellular matrix, which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion proteins including fibronectins. Thus, the rules of architecture for tissue engineering are an imitation of the laws of developmental biology and morphogenesis, and thus may be universal for all tissues, including bones and joints.

Adult↗
PubMed2000

Initiation and promotion of endochrondral bone formation by bone morphogenetic proteins: potential implications for avian tibial dyschondroplasia.

The initiation and promotion of bone morphogenesis is regulated by bone morphogenetic proteins. Morphogenesis of the skeleton is the developmental cascade of pattern formation, establishment of mirror-image bilateral symmetry, initiation and promotion of endochondral bone differentiation, and growth culminating in functional weight bearing. Implantation of demineralized bone matrix initiates a developmental cascade of endochondral bone formation that is reminiscent of the sequential bone morphogenesis in the limb bud in the embryo. The inductive agents in the demineralized bone matrix were identified, isolated and cloned, and demonstrated to be bone morphogenetic proteins (BMP). The BMP have been implicated in the pattern formation, differentiation, and regeneration of bone. Because there is a persistent defect in endochondral bone formation in the epiphysed growth plate in tibial dyschondroplasia in poultry, it is likely that BMP signaling mechanisms may be impaired.

Animals↗
PubMed2000

Long-term evaluation of bone formation by osteogenic protein 1 in the baboon and relative efficacy of bone-derived bone morphogenetic proteins delivered by irradiated xenogeneic collagenous matrices.

To investigate the long-term efficacy of irradiated recombinant human osteogenic protein 1 (hOP-1) in bone regeneration and morphogenesis, hOP-1 was combined with a bovine collagenous matrix carrier (0, 0.1, 0.5, and 2.5 mg hOP-1/g of matrix), sterilized with 2.5 Mrads of y-irradiation, and implanted in 80 calvarial defects in 20 adult baboons (Papio ursinus). The relative efficacy of partially purified bone-derived baboon bone morphogenetic proteins (BMPs), known to contain several osteogenic proteins, was compared with the recombinant hOP-1 device in an additional four baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 90 and day 365 showed that gamma-irradiated hOP-1 devices induced regeneration of the calvarial defects by day 90, although with reduced bone area compared with a previous published series of calvarial defects treated with nonirradiated hOP-1 devices. One year after application of the irradiated hOP-1 devices, bone and osteoid volumes and generated bone tissue areas were comparable with nonirradiated hOP-1 specimens. Moreover, 365 days after healing regenerates induced by 0.5 mg and 2.5 mg of irradiated hOP-1 devices showed greater amounts of bone and osteoid volumes when compared with those induced by nonirradiated hOP-1 devices. On day 90, defects treated with 0.1 mg and 0.5 mg of bone-derived baboon BMPs, combined with irradiated matrix, showed significantly less bone compared with defects receiving irradiated devices containing 0.1 mg and 0.5 mg hOP-1; 2.5 mg of partially purified BMPs induced bone and osteoid volumes comparable with the 0.1-mg and 0.5-mg hOP-1 devices. Control specimens of y-irradiated collagenous matrix without hOP-1 displayed a nearly 2-fold reduction in osteoconductive bone repair when compared with nonirradiated controls. These findings suggest that the reduction in bone volume and bone tissue area on day 90 may be caused by a reduced performance of the irradiated collagenous matrix substratum rather than to a reduction in the biological activity of the irradiated recombinant osteogenic protein. This is supported by the results of in vitro and in vivo studies performed to determine the structural integrity of the recovered gamma-irradiated hOP-1 before application in the baboon. Recoveries by high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate/ polyacrylamide gel electrophoresis (SDS/PAGE)/immunoblot analyses indicated that doses of 2.5-3 Mrads of gamma-irradiation did not significantly affect the structural integrity of the recovered hOP-1. Biological activity of the recovered hOP-1 was confirmed in vitro by showing induction of alkaline phosphatase activity in rat osteosarcoma cells (ROS) and in vivo by de novo endochondral bone formation in the subcutaneous space of the rat. These findings in the adult primate indicate that a single application of gamma-irradiated hOP-1 combined with the irradiated xenogeneic bovine collagenous matrix carrier is effective in regenerating and maintaining the architecture of the induced bone at doses of 0.5 mg/g and 2.5 mg/g of carrier matrix.

Alkaline Phosphatase↗
PubMed2000

Morphogenetic messages are in the extracellular matrix: biotechnology from bench to bedside.

The origin and evolution of multicellular metazoa was accompanied by the appearance of extracellular matrix. The demineralized extracellular matrix of bone is enriched in morphogenetic proteins that induce bone. Bone morphogenetic proteins (BMPs) are intimately bound to collagens. BMP-4 has high affinity for type-IV collagen, and other binding proteins such as noggin and chordin. Soluble morphogens are kept in the solid state by extracellular matrix. In this sense Nature used the principles of affinity matrices long before humans patented the principle of affinity chromatography.

Animals↗
PubMed1998

Androgen-dependent gene expression of bone morphogenetic protein 7 in mouse prostate.

BACKGROUND: What is the molecular basis of the osteotrophic action of prostatic metastases? Demineralized bone matrix has the potential to induce new bone formation. The identification of bone morphogenetic proteins (BMPs) as the primary inducers of new bone formation in demineralized bone matrix has set the stage for studying prostate cancer-bone interrelationships. We have hypothesized that BMPs may be expressed in prostate and may be involved in the osteotrophic actions of metastatic prostate cancer cells. METHODS: Using polymerase chain reaction (PCR)-based quantitation, this study examined the presence of BMPs in mouse prostate and their potential regulation by orchidectomy and androgen replacement. RESULTS: BMP-7 and BMP-4 genes were expressed in mouse prostate. Quantitative PCR analysis showed that the BMP-7 mRNA level was significantly decreased following orchidectomy and increased by testosterone and dihydrotestosterone. Therefore, the BMP-7 mRNA level is androgen-dependent. On the other hand, BMP-4 was expressed constitutively in the prostate. CONCLUSIONS: The regulated expression of BMP-7 mRNA in the prostate suggests that BMP-7 may explain in part the stimulation of bone formation and osteosclerosis by metastatic prostate adenocarcinoma.

Animals↗
PubMed1998

Cartilage-derived morphogenetic proteins and cartilage morphogenesis.

Cartilage morphogenesis is a prerequisite for skeletal development and maintenance. The morphogenesis of cartilage determines the shape of bones, and joints including articular cartilage, ligaments, and tendon. This article reviews the recent advances in cartilage-derived morphogenetic proteins (CDMPs) and related bone morphogenetic proteins (BMPs). Cartilage-derived morphogenetic proteins (CDMPs) are related to BMPs and are critical for cartilage and joint morphogenesis. Cartilage morphogenesis is a multistep cascade that includes factors for initiation, promotion, and maintenance of cartilage phenotype. The extracellular matrix of cartilage consists of a constellation of macromolecules such as collagens, proteoglycans, and glycoproteins. Morphogens bind to extracellular matrix components and assemble a morphogenetic scaffold. Recent advances in CDMPs may aid in articular cartilage repair and regeneration.

Animals↗
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↗
PubMed1998

Radiation-induced impairment of bone healing can be overcome by recombinant human bone morphogenetic protein-2.

Radiotherapy of head and neck tumors very often results in impaired healing of craniomaxillofacial bones in the vicinity. Management of radionecrosis of bones after radiotherapy is an important clinical challenge. Bone morphogenetic proteins (BMPs) induce new bone differentiation. The aim of this study is to investigate the potential of BMPs in ameliorating radiation-induced impaired bone repair. Two 3-mm diameter defects were created in the calvaria of rats. The defects were treated with different doses of recombinant human (rh) BMP-2 using collagen type I as a carrier. Irradiation with a single dose of 1,200 rad was performed 2 or 7 days preoperatively. Unirradiated animals served as controls. New bone formation was assessed by quantitation of radiographs of the calvaria and histology on day 21 after surgery. Untreated, unirradiated defects showed a spontaneous osseous regeneration of 90 +/- 7% of the defect area within 21 days. Irradiation of the site (1,200 rad 2 days preoperatively) resulted in a profound decrease in the bone fill of the untreated defect (5 +/- 2%). Recombinant human BMP-2 in soluble collagen type I carrier delivered to the defect resulted in a significant increase of new bone formation (34 +/- 14%, P < 0.01 for 25 micrograms rhBMP-2; 77 +/- 19% for 35 micrograms rhBMP-2, P < 0.01). Type I collagen carrier alone resulted in only 7 +/- 2% healing. In conclusion, radiation-induced impairment of calvarial repair can be overcome by rhBMP-2. Thus, the concept of BMP-2-induced regeneration has potential applications in reconstructive craniomaxillofacial surgery after irradiation.

Animals↗