Functional Benefits of Low-Molecular-Weight Collagen Peptide in Achilles Tendon and Medial Collateral Ligament Injuries and Anterior Cruciate Ligament Transection-Induced Osteoarthritis
Eunjung Choi et al. J Microbiol Biotechnol. 2025.
Abstract
Musculoskeletal disorders, such as Achilles tendinopathy and anterior cruciate ligament (ACL) injury, can cause serious impairments in physical function and daily life. In particular, ACL rupture increases the risk of osteoarthritis (OA). Collagen maintains the mechanical strength and resilience of tendons and articular cartilage, while low-molecular-weight collagen peptides (LMWCP) support tissue integrity and joint mobility. This study evaluated the efficacy of LMWCP in promoting the repair of Achilles tendon (AT) and medial collateral ligament (MCL), and preventing ACL transection (ACLT)-induced OA. In animal models, LMWCP was administered following AT and MCL injuries, as well as ACLT. LMWCP treatment in the ACLT rabbit model significantly improved cartilage integrity, reducing surface damage, proteoglycan loss, and OARSI scores. It also inhibited subchondral bone deterioration and osteophyte formation, restoring bone volume fraction, as shown by Micro-CT analysis. Moreover, LMWCP administration increased type II collagen expression while decreasing that of matrix metalloproteinases (MMPs) in cartilage tissue, and decreased inflammatory cytokine concentrations in the synovial fluid. In IL-1β-stimulated human chondrocytes, LMWCP suppressed inflammatory cytokines and MMP expression, and increased hydroxyproline content, indicating reduced collagen degradation. In the AT and MCL defect model, LMWCP promoted tissue regeneration by improving fiber arrangement, rounding of nuclei, angiogenesis, and cell density and promoting collagen deposition. These findings suggest that LMWCP may enhance joint function and tendon healing through modulation of inflammation and collagen remodeling, representing a functional ingredient for promoting tendon and ligament repair and attenuating ACLT-induced OA progression.
Keywords: Low-molecular-weight collagen peptide; achilles tendinopathy; anterior cruciate ligament; collagen; osteoarthritis.
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Conflict of interest statement
Conflict of Interest
The authors have no financial conflicts of interest to declare.
Figures Fig. 1. Low-molecular-weight collagen peptide (LMWCP) improved osteoarthritis-associated cartilage damage in an ACLT model.
After ACLT or sham surgery, rabbits were orally administered vehicle or LMWCP (200 mg/kg) once daily for 12 weeks. (A) Representative hematoxylin and eosin (H&E) staining of the tibia and femur (magnification, ×100). (B) Representative Safranin O staining images of the tibia and femur (magnification ×100). (C) Quantitative analysis of cartilage degeneration based on OARSI scores. Data represent mean ± standard deviation (n = 8). Statistical analysis was performed using t-test. ***p < 0.001, compared with sham group. ###p < 0.001, compared with ACLT group. Fig. 2. Low-molecular-weight collagen peptide (LMWCP) suppressed osteoarthritis-associated subchondral bone damage in a rabbit ACLT model.
Rabbits underwent ACLT or sham surgery and were orally administered vehicle or LMWCP (200 mg/kg) once daily for 12 weeks. (A) Representative micro-computed tomography (CT) images of subchondral bone. Quantitative micro-CT analysis of subchondral bone in the tibia (B) and femur (C). Trabecular bone volume/total volume (BV/TV), trabecular bone surface area/bone volume (BS/BV), trabecular bone number (TbN), trabecular bone thickness (TbTh), and trabecular separation (TbSp). Data represent mean ± standard deviation (n = 8). Statistical analysis was performed using t-test. *p < 0.05, **p < 0.01 and ***p < 0.001 compared with sham group. #p < 0.05 and ##p < 0.01 compared with ACLT group. Fig. 3. Low-molecular-weight collagen peptide (LMWCP) inhibits proinflammatory cytokines in IL-1β- stimulated human chondrocytes and synovial fluid from rabbit ACLT model.
(A) mRNA expression of IL-6 and IL-1β was quantified by qRT-PCR to evaluate the inhibitory effect of LMWCP on IL-1β-induced proinflammatory cytokines. Data are presented as the mean ± SD (n = 3) (B) Protein levels of IL-6 and IL-1β were measured by ELISA in synovial fluid from rabbits that underwent either ACLT or sham surgery and were treated with LMWCP (200 mg/kg) or vehicle via oral gavage once daily for 12 weeks. Data represent mean ± standard deviation (n = 8). Statistical analysis was performed one-way ANOVA followed by Duncan’s test for in vitro data and using t-test for in vivo data. a~f) The statistical significance level of the average value for each experimental group is indicated by each subgroup for p < 0.05. ***p < 0.001, compared with sham group. ###p < 0.001, compared with ACLT group. Fig. 4. Effect of low-molecular-weight collagen peptide (LMWCP) on collagen preservation in human chondrocytes and rabbit cartilage of ACLT model.
(A) Collagen degradation was assessed by measuring hydroxyproline content in IL- 1β (0.1 ng/ml)-stimulated SW1353 chondrocytes treated with different concentrations of LMWCP (100–1,000 μg/ml). Data are presented as the mean ± SD (n = 3) (B) mRNA expression of MMP-1, MMP-3, and MMP-13 was quantified by qRT-PCR to evaluate the inhibitory effect of LMWCP on IL-1β-induced MMP upregulation. Data are presented as the mean ± SD (n = 3) (C) Representative immunohistochemical images of cartilage (magnification, ×100). Quantitative analysis of type II collagen (COL II). (D) Representative immunohistochemical images of cartilage (magnification, ×100). Quantitative analysis of MMP- 13 staining. Data represent mean ± standard deviation (n = 8). Statistical analysis was performed using one-way ANOVA followed by Duncan’s test for in vitro data and using t-test for in vivo data. a~g) The statistical significance level of the average value for each experimental group is indicated by each subgroup for p < 0.05. ***p < 0.001, compared with sham group. #p < 0.05 and ###p < 0.001 compared with ACLT group. Fig. 5. LMWCP enhances tendon healing and collagen preservation in the medial collateral ligament and Achilles tendon (AT) defect model.
Rabbits underwent Achilles tendon injury and received either vehicle or LMWCP (200 mg/kg) via oral gavage once daily for six weeks. (A) Representative hematoxylin and eosin (H&E)-stained images of the areas in the AT defect (AT-D) (magnification ×100). Fiber structure, fiber arrangement, rounding of nuclei, angiogenesis, cell density, and collagen stainability were assessed in the AT. (B, C) Representative immunohistochemical images of type I collagen (COL I) and type III collagen (COL III) staining in the AT defect area (B) and medial collateral ligament defect area (C) (magnification ×100). The proportion of collagen–positive areas was quantified. Data represent mean ± standard deviation (n = 5). Statistical analysis was performed using t-test. *p < 0.05, **p < 0.01 and ***p < 0.001 compared with sham group. #p < 0.05 and ##p < 0.01 compared with AT-D and MCL-D group.
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