Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus

Onur, T.; Wu, Ruobin; Metz, Lionel N.; Dang, Alexis

doi:10.1302/2046-3758.36.2000244

Cited by 36 publications

(21 citation statements)

References 32 publications

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“…Recently, the association between T2D and increased severity of OA has been partly explained by the degradative effect of high hyperglycemia and hyperinsulinemia on cartilage in cellular and animal studies. 10–13 However, the effect has not been validated in human cartilage yet. In this study, we found a higher histological OARSI score on medial tibial plateau in diabetes group compared to non-diabetic group, which is consistent with previous findings.…”

Section: Discussionmentioning

confidence: 99%

“…As articular cartilage degradation has long been regarded as the primary characteristic of knee OA, recently the catabolic effect of high concentrations of glucose and insulin on cartilage through molecular and cellular mechanisms was the major explanation for the relationship between T2D and knee OA. 10–13 But most of these data were obtained from cellular or animal models, and the relationship has not been validated in humans yet.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

et al. 2017

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Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic (n=70) and diabetes (n=51) groups. Tibial plateaus were also collected from cadaver donors (n=20) and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase (TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International (OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP+ osteoclasts and lower number of Osterix+ osteoprogenitors and Osteocalcin+ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

et al. 2017

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“…In patients with hyperglycemia increased formation AGE (product of interaction of glucose with free amino-acid remains in proteins), especially in the tissues enriched with collagen that leads to mechanical and biomechanical change of tissues including a cartilage [18].…”

Section: Discussionmentioning

confidence: 99%

Characterization of osteoarthritis in patients with diabetes mellitus type 2

Зонова¹,

Лыков²,

Trifonova³

et al. 2016

Integr Mol Med

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Investigation of the clinical and pathogenesis aspects of osteoarthritis in combinations with diabetes mellitus type 2. Were studied 80 patients with osteoarthritis, 52 of them has a comorbidity disease such as diabetes mellitus type 2. Were investigated the clinical and radiological signs of disease severity, the levels of cytokines, NO, leptin, and CRP in serum, and levels of blood glucose, and levels of glycated hemoglobin, and SSE. Were found significant differences in body weight, data of ESR, features functional status of the joints and the quality of life in patients with osteoarthritis in combination with type 2 diabetes compared with those without the metabolic disturbance. Moreover, in patients with osteoarthritis of comorbidity for T2DM was established elevated level of IL-6, IL-18, NO and leptin in serum. Were determined differences in the features of the clinical symptoms of osteoarthritis in patients with type 2 diabetes based on blood glucose level, and data of glycated hemoglobin. Were obtained some correlations between of the levels of cytokines in the blood serum with the parameters of the functional status of the joints, and with the quality of life in patients with osteoarthritis in combination with type 2 diabetes. Osteoarthritis in combinations with diabetes mellitus type 2 characterized by a more pronounced severity of clinical symptoms, and functions impairment.

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“…75 The macroanatomy of cartilage tissue during prolonged metabolic stress and oxidative stress exhibits early changes in the gliding zone, with a thinning of the proteoglycan and collagen layers as well as disorganization of collagen fibre orientation. 64,76 These changes are followed by more extensive degenerative changes in the deeper transitional and radial zones. Microanatomically, a loss of matrix proteins and chondrocytes is observed in all these zones.…”

Section: Oxidative Stress and Cartilage Structurementioning

confidence: 99%

Consequences of metabolic and oxidative modifications of cartilage tissue

2015

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A hallmark of chronic metabolic diseases, such as diabetes and metabolic syndrome, and oxidative stress, as occurs in chronic inflammatory and degenerative conditions, is the presence of extensive protein post-translational modifications, including glycation, glycoxidation, carbonylation and nitrosylation. These modifications have been detected on structural cartilage proteins in joints and intervertebral discs, where they are known to affect protein folding, induce protein aggregation and, ultimately, generate microanatomical changes in the proteoglycan–collagen network that surrounds chondrocytes. Many of these modifications have also been shown to promote oxidative cleavage as well as enzymatically-mediated matrix degradation. Overall, a general picture starts to emerge indicating that biochemical changes in proteins constitute an early event that compromises the anatomical organization and viscoelasticity of cartilage, thereby affecting its ability to sustain pressure and, ultimately, impeding its overall bio-performance.

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Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus

Cited by 36 publications

References 32 publications

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Characterization of osteoarthritis in patients with diabetes mellitus type 2

Consequences of metabolic and oxidative modifications of cartilage tissue

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