Molecular and cellular mechanisms of osteoarthritis in experimental arterial hypertension and hyperlipidemia

Abstract

Purpose: To study the role of vascular endothelial growth factor (VEGF-A), adiponekin (Adipo) and matrix metalloproteinase-9 (MMP-9) in remodeling of articular cartilage (AC) and subchondral bone (SCB) in experimental arterial hypertension (AH) and hyperlipidemia (HL). Methods: An experimental study was carried out on 18 adult males of purebred guinea pigs (28-30 weeks old, weight 750-900 g), which were divided into 3 groups of 6 individuals each: in the first group AH was modeled, in the second group - HL, the third group was intact animals (control). To assess the reproduction of a qualitative model in animals, the level of blood pressure, total cholesterol, and body weight were determined. On the 60th day all the animals were removed from the experiment, the tissues of the knee joints of the hind (hock) paws were taken. Immunohistochemical reaction was performed according to the standard protocol using primary species-specific antibodies to VEGF-A, Adipo, MMP-9. Results: In the control group of animals, the immunohistochemical reaction of AC to VEGF-A was determined as single low-intensity precipitates in the region of the pericellular matrix of the basal layers of chondrocytes. In the SCB, single precipitates of vascular endothelial growth factor were found in the central parts of the haversian systems. A high intensity response to VEGF was observed in the red bone marrow. In the group of animals with hypertension, the reaction of articular cartilage on VEGF-A was determined in all areas of cartilage. Its greatest intensity was in the perchondrium, on the periphery of the zones of destruction of the articular cartilage. Within the limits of the fuzzy osteochondral line, elements of ectopic vascular invasion were determined by the type of non-vascular expansion in AC with a positive response to VEGF. Maximum expression of VEGF-A was found in the region of contact of the subchondral bone with destruction of articular cartilage. In hyperlipidemia, AC was positive for VEGF-A in the area of chondrocyte lacunae of hypertrophied chondrocytes in all layers of the cartilage plate. In SCB, the vascular endothelial growth factor was found in the area of osteogenesis imperfecta foci, the red bone marrow. The histochemical reaction of AC and SCB to adiponectin in intact animals was practically not determined. There were isolated low-intensity precipitates. Tissue expression of Adipo in animals with AH in AC was determined in the form of multiple precipitates with a high density of IHC-reaction with a maximum response in the basal regions of the cartilage plate. In the SCB with experimental hypertension, adiponectin tissue precipitates were found in the area of haversian systems, osteochondral communication. In hyperlipidemia in AC, a positive reaction to Adipo was found in the area of chondrocyte lacunae predominantly in the upper and middle layers of the cartilage plate. in all layers of the cartilage plate. Under conditions of lipid metabolism impairment, the Adipo SCB was defined as diffuse deposits in the communicative regions with basal soreness, in the zones of the haversian systems and the bone matrix. The tissue response to MMP-9 SCB and AC in the control group was not very pronounced, showing up as single low-intensity cell-cell precipitates. Under the conditions of experimental arterial hypertension in the articular cartilage, MMP-9 was determined in the subcellular matrix of hypertrophied chondrocytes, mainly in the middle layer. In SCB, a positive response to matrix metalloproteinase-9 was found in the area of angiovasal integration into the basal cartilage, in the centers of imperfect osteogenesis. The highest expression density of MMP-9 was determined in the group of animals with HL. Deposits of MMP-9 were found in cartilage tissue, mainly in the upper and middle sections. In SCB at HL, the tissue reaction to the matrix metalloproteinase-9 was also detected in the foci of ectopic angiogenesis. Conclusions: The results of the study allowed to establish that under the influence of systemic AH and HL in the articular cartilage and subchondral bone cell stress develops, caused by endothelium-dependent dysmetabolism. In the present study, it was shown that extravasal expression of VEGF-A is observed in experimental AH, most pronounced in SCB. In addition, moderate expression of adiponectin and MMP-9 in the SCB is noted. In systemic AH, in experimental conditions, VEGF-A is overexpressed in articular cartilage. In addition to this, in addition to this, Adipo and MMP-9 are highly expressed in SCB. It is established that angiogenic factors contribute to the neovascularization of cartilage, non-adaptive osteoregeneration of SCB. At the same time, remodeling of the tissues of the joints is obviously provided by tissue metalloproteinases. The data obtained allow us to makethe assumption that SCB and AC are target organs of cardiovascular factors.