Upper Zone of Growth Plate and Cartilage Matrix (UCMA) Levels in Patients with Chronic Kidney Disease

Abstract Chronic kidney disease (CKD) is an important health problem across the world affecting the adult population with an enormous social and economic burden. Calcium regulation is also affected in patients with CKD, and related to several disorders including vascular calcifications, mineral bone disorders, and cardiovascular diseases (CVD). Upper zone of growth plate and cartilage matrix (UCMA) is vitamin K-dependent protein (VKDP) and acts as a calcification inhibitor in the cardiovascular system. The molecular mechanism of UCMA action remains unclear in CKD. In the current study, we aimed to investigate serum total UCMA levels and its association with calcium metabolism parameters in CKD patients including hemodialysis (HD) patients. Thirty-seven patients with CKD stage 3-5, 41 HD patients, and 34 healthy individuals were enrolled in this cross-sectional study. Serum UCMA and calcification related protein levels (Matrix Gla Protein (MGP), Osteocalcin (OC), and Fetuin-A) were analyzed with enzyme-linked immunosorbent assay (ELISA). Calcium mineral disorder parameters (Serum Ca, P, iPTH) were quantified with routine techniques. We, for the first time, report the potential biomarker role of UCMA in CKD including HD. Serum total UCMA levels were significantly higher in patients with CKD including HD patients than the healthy controls. Also, serum UCMA levels showed negative correlations with serum calcium, and eGFR, while showed positive relationships with P, iPTH, MGP, OC. Increased total UCMA levels may have a role in the Ca metabolism disorder and related to the pathogenesis of Vascular Calcification in patients with CKD.

Effects of physical exercise on the cartilage of ovariectomized rats submitted to immobilization / Efeitos do exercício físico sobre a cartilagem de ratas ooforectomizadas submetidas à imobilização

ABSTRACT Objective To analyze the effects of physical exercise on cartilage histomorphometry in osteoporosis-induced rats subjected to immobilization. Methods We used 36 Wistar rats that were separated into six groups: G1, G2 and G3 submitted to pseudo-oophorectomy, and G4, G5 and G6 submitted to oophorectomy. After 60 days at rest, G2, G3, G5 and G6 had the right hind limbs immobilized for 15 days, followed by the same period in remobilization, being free in the box to G2 and G5, and climb ladder to G3 and G6. At the end of the experiment, the rats were euthanized, their tibias bilaterally removed and submitted to histological routine. Results There was significant increase in thickness of the articular cartilage (F(5;29)=13.88; p<0.0001) and epiphyseal plate (F(5;29)=14.72; p<0.0001) as the number of chondrocytes (F(5;29)=5.11; p=0.0021) in ovariectomized rats, immobilized and submitted to exercise. In the morphological analysis, degeneration of articular cartilage with subchondral bone exposure, loss of cellular organization, discontinuity of tidemark, presence of cracks and flocculation in ovariectomized, immobilized and free remobilization rats were found. In ovariectomized and immobilized remobilization ladder rats, signs of repair of the cartilaginous structures in the presence of clones, pannus, subcortical blood vessel invasion in the calcified zone, increasing the amount of isogenous groups and thickness of the calcified zone were observed. Conclusion Exercise climb ladder was effective in cartilaginous tissue recovery process damaged by immobilization, in model of osteoporosis by ovariectomy in rats.

RESUMO Objetivo Analisar os efeitos do exercício físico sobre a histomorfometria da cartilagem de ratas induzidas à osteoporose e submetidas à imobilização. Métodos Foram utilizadas 36 ratas Wistar separadas em seis grupos: G1, G2 e G3 submetidas à pseudo-ooforectomia e G4, G5 e G6, à ooforectomia. Após 60 dias em repouso, G2, G3, G5 e G6 tiveram o membro posterior direito imobilizado por 15 dias, seguido pelo mesmo período em remobilização, sendo livres na caixa para G2 e G5, e de subida em escada para G3 e G6. Ao final do experimento, as ratas foram eutanasiadas, e suas tíbias foram retiradas bilateralmente e submetidas à rotina histológica. Resultados Houve aumento significativo de espessura da cartilagem articular (F(5;29)=13,88; p<0,0001) e da placa epifisária (F(5;29)=14,72; p<0,0001), bem como do número de condrócitos (F(5;29)=5,11; p<0,0021) em ratas ooforectomizadas, imobilizadas e submetidas ao exercício em escada. Nas análises morfológicas, verificaram-se degeneração da cartilagem articular com exposição de osso subcondral, perda da organização celular, descontinuidade da tidemark, presença de fissuras e floculações em ratas ooforectomizadas, imobilizadas e com remobilização livre. Nas ratas ooforectomizadas, imobilizadas e com remobilização em escada, observaram-se sinais de reparação das estruturas cartilaginosas com presença de clones, pannus, invasão de vasos sanguíneos subcorticais na zona calcificada, aumento da quantidade de grupos isógenos e espessura da zona calcificada. Conclusão O exercício físico de subida em escada mostrou-se efetivo no processo de recuperação do tecido cartilaginoso danificado pela imobilização, em modelo de osteoporose por ooforectomia em ratas.

Response of the growth plate of uremic rats to human growth hormone and corticosteroids

Children with chronic renal failure in general present growth retardation that is aggravated by corticosteroids. We describe here the effects of methylprednisolone (MP) and recombinant human growth hormone (rhGH) on the growth plate (GP) of uremic rats. Uremia was induced by subtotal nephrectomy in 30-day-old rats, followed by 20 IU kg-1 day-1 rhGH (N = 7) or 3 mg kg-1 day-1 MP (N = 7) or 20 IU kg-1 day-1 rhGH + 3 mg kg-1 day-1 MP (N = 7) treatment for 10 days. Control rats with intact renal function were sham-operated and treated with 3 mg kg-1 day-1 MP (N = 7) or vehicle (N = 7). Uremic rats (N = 7) were used as untreated control animals. Structural alterations in the GP and the expression of anti-proliferating cell nuclear antigen (PCNA) and anti-insulin-like growth factor I (IGF-I) by epiphyseal chondrocytes were evaluated. Uremic MP rats displayed a reduction in the proliferative zone height (59.08 ± 4.54 vs 68.07 ± 7.5 æm, P < 0.05) and modifications in the microarchitecture of the GP. MP and uremia had an additive inhibitory effect on the proliferative activity of GP chondrocytes, lowering the expression of PCNA (19.48 ± 11.13 vs 68.64 ± 7.9 percent in control, P < 0.0005) and IGF-I (58.53 ± 0.96 vs 84.78 ± 2.93 percent in control, P < 0.0001), that was counteracted by rhGH. These findings suggest that in uremic rats rhGH therapy improves longitudinal growth by increasing IGF-I synthesis in the GP and by stimulating chondrocyte proliferation.

MRI characteristics and transverse relaxation time measurements in normal growing cartilage / 华中科技大学学报（医学）（英德文版）

To determine the characteristics of magnetic resonance (MR) signals of normal growing cartilage and identify the difference in transverse relaxation times between physeal and epiphyseal cartilage in vivo. 24 distal femora of 12 two-week-old piglets were imaged on a 1.5 Tesla GE MR scanner. Comparison was made between signal intensity on MR images and the structure shown in corresponding histologic sections. T2 values were measured in eight piglets by means of multiecho spin-echo sequences. Our results showed that MR imaging delineated five regions between the secondary ossification center and the metaphysis, which histologically correspond to the zone of provisional calcification of the secondary ossification center, physis of the secondary ossification center, epiphyseal cartilage, physis and zone of provisional calcification. The T2 value in the physeal cartilage was much larger than that in the epiphyseal cartilage (P<0.05). It is concluded that MRI findings could differentiate the different regions of growing cartilage. T2 is longer in physeal than in epiphyseal cartilage, perhaps reflecting differences in water binding by proteoglycans.