Abstract:
Background: Connective tissue disorders such as rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus are characterized by chronic inflammation and collagen degradation, which contribute to tissue damage and disease progression. Specific Background: Collagen degradation biomarkers, including matrix metalloproteinases (MMP-1, MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), and inflammatory markers (CRP, TNF-α), reflect the extent of tissue remodeling and inflammation. However, limited studies comprehensively evaluate their diagnostic and prognostic value in these disorders. Knowledge Gap: There is insufficient evidence comparing the levels of these biomarkers between patients with connective tissue disorders and healthy individuals, particularly regarding their role in disease monitoring and progression. Aims: This study aims to assess and compare collagen degradation biomarkers (MMP-1, MMP-9, TIMP-1, CTX, CRP, TNF-α) between patients with connective tissue disorders and healthy controls to explore their diagnostic and prognostic significance. Results: Patients exhibited significantly elevated levels of MMP-1, MMP-9, TIMP-1, CTX, CRP, and TNF-α compared to healthy controls (p < 0.05), suggesting increased collagen turnover and chronic inflammation. BMI was also significantly higher in patients (p = 0.003). Novelty: This study provides comprehensive comparative data on multiple biomarkers, highlighting the simultaneous elevation of collagen degradation and inflammatory markers as potential indicators for disease severity. Implications: These findings suggest that assessing collagen degradation biomarkers can enhance early diagnosis, monitor disease progression, and guide therapeutic strategies for connective tissue disorders.
Highlights:
- Collagen biomarkers indicate tissue damage in connective tissue disorders.
- Compare collagen biomarkers in patients and healthy controls for diagnostic value.
- Biomarkers are significantly elevated in patients, indicating increased collagen turnover and inflammation.
Keyword: Collagen degradation, MMPs (Matrix metalloproteinases), TIMP-1 (Tissue inhibitor of metalloproteinases), CTX (C-terminal telopeptide of collagen), Chronic inflammation, Connective tissue disorders
References
M. A. Karsdal et al., "Profiling and targeting connective tissue remodeling in autoimmunity—a novel paradigm for diagnosing and treating chronic diseases," Autoimmun. Rev., vol. 20, no. 1, p. 102706, 2021.
D. Singh, V. Rai, and D. K. Agrawal, "Regulation of collagen I and collagen III in tissue injury and regeneration," Cardiol. Cardiovasc. Med., vol. 7, no. 1, p. 5, 2023.
M. J. Mienaltowski et al., "Basic structure, physiology, and biochemistry of connective tissues and extracellular matrix collagens," in Prog. Heritable Soft Connect. Tissue Dis., 2021, pp. 5–43.
Di Martino et al., "Collagen VI in the musculoskeletal system," Int. J. Mol. Sci., vol. 24, no. 6, p. 5095, 2023.
Mixon, A. S. Bahar-Moni, and T. R. Faisal, "Mechanical characterization of articular cartilage degraded combinedly with MMP-1 and MMP-9," J. Mech. Behav. Biomed. Mater., vol. 129, p. 105131, 2022.
P. Zhou et al., "The imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 contributes to collagen deposition disorder in diabetic non-injured skin," Front. Endocrinol., vol. 12, p. 734485, 2021.
V. Pulito-Cueto et al., "Matrix metalloproteinases and their tissue inhibitors as upcoming biomarker signatures of connective tissue diseases-related interstitial lung disease: towards an earlier and accurate diagnosis," Mol. Med., vol. 31, p. 70, 2025.
N. Faisal et al., "Histological and cytokine-based biomarkers in the early diagnosis of cancer," Indones. J. Health Sci. Med., vol. 2, no. 2, pp. 10–21070, 2025.
D. Radzki et al., "Matrix metalloproteinases in the periodontium—vital in tissue turnover and unfortunate in periodontitis," Int. J. Mol. Sci., vol. 25, no. 5, p. 2763, 2024.
F. J. A. Hagemans et al., "An anterior cruciate ligament rupture increases levels of urine N-terminal cross-linked telopeptide of type I collagen, urine C-terminal cross-linked telopeptide of type II collagen, serum aggrecan ARGS neoepitope, and serum tumor necrosis factor–α," Am. J. Sports Med., vol. 49, no. 13, pp. 3534–3543, 2021.
Traboulsi-Garet et al., "Is serum C-terminal telopeptide cross-link of type 1 collagen a reliable parameter for predicting the risk of medication-related osteonecrosis of the jaws? A systematic review and meta-analysis of diagnostic test accuracy," Clin. Oral Investig., vol. 26, no. 3, pp. 2371–2382, 2022.
Y. Nazir et al., "High efficiency in vitro wound healing of Dictyophora indusiata extracts via anti-inflammatory and collagen stimulating (MMP-2 inhibition) mechanisms," J. Fungi, vol. 7, no. 12, p. 1100, 2021.
T. He et al., "Serum and urinary biomarkers of collagen type‐I turnover predict prognosis in patients with heart failure," Clin. Transl. Med., vol. 11, no. 1, p. e267, 2021.
L. Necula et al., "Collagen family as promising biomarkers and therapeutic targets in cancer," Int. J. Mol. Sci., vol. 23, no. 20, p. 12415, 2022.
F. Pamuk and A. Kantarci, "Inflammation as a link between periodontal disease and obesity," Periodontol. 2000, 2022.
Lateef, N. Nasser, and O. Mohsein, "The relationships between Aplein, Vaspin and thyroid hormone levels in obese diabetic and non-diabetic women," J. Exp. Clin. Med., vol. 41, no. 2, pp. 239–245, 2024.
T. V. Rohm, D. T. Meier, J. M. Olefsky, and M. Y. Donath, "Inflammation in obesity, diabetes, and related disorders," Immunity, 2022.
O. V. Badulescu et al., "Biomarkers involved in the pathogenesis of hemophilic arthropathy," Int. J. Mol. Sci., vol. 25, no. 18, p. 9897, 2024.
L. M. Batty et al., "The role of biomarkers in predicting outcomes of anterior cruciate ligament reconstruction: A systematic review," Orthop. J. Sports Med., vol. 12, no. 10, p. 23259671241275072, 2024.
J. Jarecki et al., "Concentration of selected metalloproteinases and osteocalcin in the serum and synovial fluid of obese women with advanced knee osteoarthritis," Int. J. Environ. Res. Public Health, vol. 19, no. 6, p. 3530, 2022.
Bud et al., "Challenges and perspectives regarding the determination of gingival crevicular fluid biomarkers during orthodontic treatment: A narrative review," Medicina, vol. 60, no. 12, p. 2004, 2024.
N. J. Hussein, "The novel regulatory roles of TRAPPC9 and L-Plastin in osteoarthritis," 2021.
H. C. Hasselbalch et al., "Revisiting circulating extracellular matrix fragments as disease markers in myelofibrosis and related neoplasms," Cancers, vol. 15, no. 17, p. 4323, 2023.
J. Stanimirovic et al., "Role of C‐reactive protein in diabetic inflammation," Mediators Inflamm., 2022.
Saleh et al., "Association of TNF-α G-308 a promoter polymorphism with the course and outcome of COVID-19 patients," Immunol. Investig., vol. 51, no. 3, pp. 546–557, 2022.
A. Hamad, H. M. Mustafa, and O. A. Mohsein, "Detection of the levels of immune cytokines (IL4, IL5, TNF-α) in school-age and preschoolers with an Ascaris lumbricoides infection," J. Parasit. Dis., vol. 48, no. 4, pp. 782–787, 2024.
R. Mardani et al., "Association between serum inflammatory parameters and the disease severity in COVID‐19 patients," J. Clin. Lab. Anal., vol. 36, no. 1, p. e24162, 2022.