Pentti Rokkanen

Increased protocollagen proline hydroxylase activity in synovial tissue in rheumatoid arthritis

Abstract Protocollagen proline hydroxylase activity was assayed in biopsy specimens of human synovial tissue. The enzyme required ascorbate, α-ketoglutarate, ferrous iron and molecular oxygen for its activity. The activity, determined from synovial tissue of 18 patients with rheumatoid arthritis, was increased as compared with values obtained from control patients.

Cathepsin G and alpha 1-antichymotrypsin in the local host reaction to loosening of total hip prostheses.

The tissue localization and content of the proteolytic enzyme cathepsin G and its inhibitor alpha 1-antichymotrypsin were studied in the local host reaction to loosening of total hip-replacement prostheses in eleven patients and were compared with those in samples of non-inflammatory tissue from the synovial capsule obtained during arthroscopies of the knee. Immunostaining demonstrated cellular localization of cathepsin G in 71 per cent of monocyte or macrophage-like cells and in 46 per cent of fibroblast-like cells in the samples of interface tissue between the bone and the loose acetabular component obtained at the time of the total hip replacements, and in 59 and 42 per cent, respectively, in the samples of pseudocapsular tissue obtained at the same time, whereas the synovial lining cells in the samples of non-inflammatory tissue from the synovial capsule revealed only a slight immunoreactivity to cathepsin G. Cathepsin-G activity was also measured with synthetic succinyl-alanine-alanine-proline-phenylalanine-paranitroanilide as a substrate, the degradation of which was monitored spectrophotometrically. In accordance with results from immunohistochemical studies, cathepsin-G activity was found in the samples of interface tissue (31.6 international units per liter) and the samples of pseudocapsular tissue (15.5 international units per liter) obtained during the total hip replacements, whereas the level of cathepsin-G was low in the samples of non-inflammatory synovial capsular tissue (2.5 international units per liter). Cathepsin-G activity in the samples of pseudosynovial fluid obtained at the time of the total hip replacements was low (2.4 international units per liter), although immunoblot analysis showed marked immunoreactive cathepsin G in the samples of pseudosynovial fluid. This low activity of cathepsin G might be explained by the presence of alpha 1-antichymotrypsin, which was detected by laser nephlometric immunoassay and immunoblot analysis. These results demonstrate increased concentration of cathepsin G locally in the tissues around loose total hip-replacement prostheses. Because cathepsin G is not only able to act on extracellular matrix components (such as gelatin, proteoglycan, elastin, and laminin) at a physiological pH but also is able to activate collagenase, gelatinase, and stromelysin proenzymes, to inactivate tissue inhibitor of metalloproteinases, and to modulate tumor necrosis factor-alpha, it may play an important role in the degradation of periprosthetic connective tissue and in the lysis of bone around the implant, thus contributing to the loosening of prostheses.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of transforming growth factor-β1, released from a bioabsorbable self-reinforced polylactide pin, on a bone defect

Transforming growth factor-beta 1 (TGF-beta1)is a polypeptide growth factor which has been shown to increase bone formation in experimental studies. In this study it was combined to a bioabsorbable self-reinforced poly-LD-lactic acid fracture fixation pin. To assess the effect of TGF-beta1 on the healing of a bone defect, the pins were implanted in the rat distal femur next to a bone defect filled with a viscose cellulose sponge. The pins used in the study group (13 rats) contained 50 microg of TGF-beta1, whereas in the control group of nine rats an identical pin without the growth factor was used. In the histologic examination at 1, 3 and 6 weeks no difference was detected in the amount of bone inside the viscose cellulose sponge between the rats treated with TGF-beta1 and those with no added growth factor. At 3 weeks there was more fibroblast-rich mesenchymal tissue inside the viscose cellulose sponge in the rats treated with TGF-beta1. In the radiographic examination at 3 weeks there was an increase in the amount of new periosteal bone on the bone defect in the TGF-beta1-treated rats.

The Normal Repair of Experimental Fractures a Histo-Quantitative Study of Rats

(1965). The Normal Repair of Experimental Fractures a Histo-Quantitative Study of Rats. Acta Orthopaedica Scandinavica: Vol. 36, No. 3, pp. 221-229.

Collagenolytic activity in rheumatoid synovial tissue

Abstract Collagenolytic activity in synovial tissue was studied by measuring the degradation of collagen in normal and rheumatoid synovial tissue samples. In the assay the 6000-g pellet of the tissue homogenate was incubated in neutral buffer in the presence of Ca2+ at 37° for 20 h. Released hydroxyproline-containing material was taken as the measure of collagenolytic activity. The mean value of collagenolytic activity in the rheumatoid arthritis group was about 6–7 times that of controls. High values were found in patients having elevated rheumatoid factor titres. The increased collagenolytic activity in rheumatoid synovial tissue suggests increased breakdown of collagen in the diseased synovium. The high collagenolytic activity in the synovium may be connected with the local tissue destruction in the joint.

Lactate dehydrogenase in the synovial tissue in rheumatoid arthritis: total activity and isoenzyme composition.

Total lactate dehydrogenase activity in the synovial tissue from 19 patients with rheumatoid arthritis and from 13 control subjects was measured. In addition, isoenzyme pattern and the subunit M percentage were determined. Total enzyme activity in synovium was increased about two-fold in rheumatoid arthritis when compared to controls. The main LDH isoenzymes both in controls and m rheumatoid arthritis were LDH4 and LDH5, the most cathodically migrating ones. Increased LDH activity was observed in all isoenzyme fractions, and the isoenzyme pattern in rheumatoid synovial tissue did not differ from that in specimens from control subjects. Consequently, no difference m the subunit M percentage, calculated from the isoenzyme pattern, could be observed. The results suggest that anaerobic metabolism is increased in the synovial tissue in rheumatoid arthritis.

Bone remodelling in the pores and around load bearing transchondral isoelastic porous-coated glassy carbon implants: Experimental study in rabbits

Cylinders of porous-coated glassy carbon were implanted into drill holes made through the articular surface of the medial condyle of both tibiae of ten rabbits for six and 12 weeks. Bone ingrowth and remodelling was examined by radiographic, histologic, oxytetracycline-fluorescence and microradiographic methods. Bone ingrowth into pores and load bearing implants was seen by all examination methods. Bone ingrowth occurred earlier when the pores were facing cancellous bone than cortical bone. Appositional bone formation occurred on the trabeculae a few millimetres from the interface during the early phase of remodelling at six weeks. At 12 weeks resorptive remodelling had occurred both in the surroundings and in those pores that face cancellous bone, whereas the amount of bone still increased in the pores facing cortical bone. In its porous-coated form glassy carbon functions well as a frame for ingrowing bone and it shows good osteoconductivity. Its mechanical properties are suitable for functioning as a structural bone substitute in places where the loads are mainly compressive. The difference between findings at six and 12 weeks indicated physiologic stress distribution and the adverse effects of stiff materials on bone remodelling were avoided by using this isoelastic material.