Polypeptides for cartilage repair, compositions and uses thereof

Abstract

The present application relates to a kind of polypeptide for cartilage repair and its composition and application, belong to bone injury repair technical field.The polypeptide is polypeptide PG155, and the experimental results of the present application show that it can repair cartilage damage caused by osteoarthritis to some extent.Further research shows that the special exosome (PG155-Exo) produced by polypeptide PG155 pretreatment bone marrow mesenchymal stem cells combined with polypeptide PG155, can significantly enhance the therapeutic effect, and show obvious synergistic effect.This synergistic effect makes the cartilage repair effect significantly better than single therapy, and provides more efficient treatment scheme for osteoarthritis patients.

Description

Technical Field

[0001] This invention belongs to the field of bone injury repair technology, and particularly relates to a polypeptide for cartilage repair, its composition, and its application. Background Technology

[0002] Osteoarthritis (OA) is a chronic degenerative disease characterized by the degeneration and destruction of articular cartilage. Its pathological process is complex and diverse, involving not only cartilage degeneration, ulceration, and loss, but also a series of secondary changes such as synovial inflammation and subchondral bone plate sclerosis. Among these pathological changes, cartilage damage, due to its irreversibility and the difficulty of treatment, has become a core issue in clinical research. Articular cartilage is a highly specialized tissue whose main function is to reduce joint friction and absorb mechanical stress. However, because cartilage itself lacks blood vessels, nerves, and lymphatic systems, its self-repair capacity is extremely limited.

[0003] In our previous research (application number: CN202410805667.2), we discovered a peptide PG155 (N-terminal sequence YTYQKEGLARVLQNN) that can effectively inhibit chondrocyte ferroptosis induced by interleukin-1β (IL-1β), thus providing a new approach for the prevention and treatment of osteoarthritis. However, although previous studies have clarified the potential of peptide PG155 in the prevention and treatment of osteoarthritis, its applicability in treating osteoarthritic cartilage damage and how to better realize its application in cartilage repair have not yet been thoroughly explored. Summary of the Invention

[0004] The purpose of this invention is to provide a polypeptide for cartilage repair, its composition and application, thereby expanding the application scope of polypeptide PG155 in the treatment of cartilage damage in osteoarthritis, and achieving synergistic treatment of cartilage damage in osteoarthritis by combining it with specially treated exosomes.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] First, the present invention provides the use of polypeptide PG155 in the preparation of a medicament for treating cartilage damage in osteoarthritis, wherein the N-terminal sequence of polypeptide PG155 is YTYQKEGLARVLQNN.

[0007] Preferably, in the drug, the effective dose of the polypeptide PG155 is 0.5-1 mg / kg per dose;

[0008] The solvent for the drug is physiological saline;

[0009] The drug is delivered via intra-articular injection into the knee joint.

[0010] Second, the present invention provides the use of a polypeptide composition in the preparation of a medicament for the synergistic treatment of cartilage damage in osteoarthritis, the polypeptide composition comprising polypeptide PG155 and PG155-Exo exosomes, wherein the N-terminal sequence of polypeptide PG155 is YTYQKEGLARVLQNN.

[0011] The PG155-Exo exosomes are exosomes produced by bone marrow mesenchymal stem cells pretreated with the peptide PG155.

[0012] Preferably, in the polypeptide composition, the mass ratio of the polypeptide PG155 to the PG155-Exo exosome is 1-4:1.

[0013] Preferably, the PG155-Exo exosomes are prepared by the following method:

[0014] (1) Bone marrow mesenchymal stem cells were cultured for 24 hours in DMEM medium containing 250 µg / mL polypeptide PG155 and fetal bovine serum with exosomes removed by ultracentrifugation;

[0015] (2) Replace with serum-free DMEM medium and continue culturing for 48 hours, then collect the supernatant;

[0016] (3) The collected supernatant was subjected to low-speed centrifugation, membrane filtration, high-speed centrifugation and ultracentrifugation in sequence to precipitate and purify the exosomes;

[0017] (4) After resuspending in PBS, centrifuge again to obtain PG155-Exo exosomes.

[0018] Preferably, in the drug, the effective dose of the polypeptide composition is 1-1.5 mg / kg per dose;

[0019] The polypeptide composition is formulated in the following amounts: 1 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes, 0.5 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes, 0.8 mg / kg polypeptide PG155 and 0.2 mg / kg PG155-Exo exosomes, or 0.6 mg / kg polypeptide PG155 and 0.4 mg / kg PG155-Exo exosomes.

[0020] Preferably, the solvent for the drug is physiological saline; and the drug is delivered by intra-articular injection into the knee joint.

[0021] Third, the present invention provides a polypeptide composition for synergistic treatment of cartilage damage in osteoarthritis, the polypeptide composition being composed of polypeptide PG155 and PG155-Exo exosomes;

[0022] The N-terminal sequence of the polypeptide PG155 is YTYQKEGLARVLQNN;

[0023] The PG155-Exo exosomes are exosomes produced by bone marrow mesenchymal stem cells pretreated with the peptide PG155;

[0024] In the polypeptide composition, the mass ratio of the polypeptide PG155 to the PG155-Exo exosome is 1-4:1.

[0025] Preferably, the PG155-Exo exosomes are prepared by the following method:

[0026] (1) Bone marrow mesenchymal stem cells were cultured for 24 hours in DMEM medium containing 250 µg / mL polypeptide PG155 and fetal bovine serum with exosomes removed by ultracentrifugation;

[0027] (2) Replace with serum-free DMEM medium and continue culturing for 48 hours, then collect the supernatant;

[0028] (3) The collected supernatant was subjected to low-speed centrifugation, membrane filtration, high-speed centrifugation and ultracentrifugation in sequence to precipitate and purify the exosomes;

[0029] (4) After resuspending in PBS, centrifuge again to obtain PG155-Exo exosomes.

[0030] Preferably, the effective dose of the polypeptide composition is 1-1.5 mg / kg per dose;

[0031] The polypeptide composition is formulated in the following amounts: 1 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes, 0.5 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes, 0.8 mg / kg polypeptide PG155 and 0.2 mg / kg PG155-Exo exosomes, or 0.6 mg / kg polypeptide PG155 and 0.4 mg / kg PG155-Exo exosomes.

[0032] The polypeptide composition is delivered via intra-articular injection into the knee joint.

[0033] The beneficial effects of this invention are as follows:

[0034] First, this invention clarifies for the first time the role of peptide PG155 in the treatment of osteoarthritis-related cartilage damage. This discovery provides a new drug option for the treatment of osteoarthritis.

[0035] Secondly, compared to using peptide PG155 alone, this invention creatively combines peptide PG155 with PG155-Exo exosomes. Experimental results show that the combined treatment significantly reduces Mankin's score and restores cartilage thickness, demonstrating a significant synergistic effect. This synergistic effect makes the cartilage repair effect significantly better than monotherapy, providing a more efficient treatment option for patients with osteoarthritis. Attached Figure Description

[0036] Figure 1 Mankin's score results for the therapeutic effect of peptide PG155 on cartilage damage in rats with osteoarthritis;

[0037] Figure 2 Mankin's score results for the therapeutic effect of exosomes combined with peptide PG155 on cartilage damage in rats with osteoarthritis;

[0038] Figure 3 Electron microscopy results of exosomes from ordinary bone marrow mesenchymal stem cells and PG155-Exo exosomes;

[0039] Figure 4 Mankin's score results for the therapeutic effect of PG155-Exo exosomes combined with peptide PG155 on cartilage damage in rats with osteoarthritis;

[0040] Figure 5 The therapeutic effect of PG155-Exo exosomes combined with peptide PG155 on cartilage thickness in rats with osteoarthritis;

[0041] Figure 6 Mankin's score results showing the therapeutic effects of different mass ratios of combined drugs on cartilage damage in rats with osteoarthritis.

[0042] Figure 7 To investigate the therapeutic effects of different mass ratios of combined drugs on cartilage thickness in rats with osteoarthritis. Detailed Implementation

[0043] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0044] Example 1

[0045] To detect the therapeutic effect of peptide PG155 on osteoarthritis-related cartilage damage.

[0046] Forty-eight 4-week-old Sprague-Dawley (SD) rats, weighing approximately 200g, were used in this experiment. All animals were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. The rats underwent acclimatization feeding in the laboratory environment for 7 days to ensure they adapted to the experimental environment and maintained good health. During the acclimatization feeding period, the rats were housed under standard temperature (22 ± 2℃), humidity (50 ± 10%), and light conditions (12-hour light / 12-hour dark cycle), with free access to standard feed and drinking water.

[0047] After the acclimatization period, 36 rats were randomly selected from 48 rats for the construction of an osteoarthritis model. Before the experiment, the selected rats were anesthetized with isoflurane or sodium pentobarbital. Once fully anesthetized, the rats were fixed to the operating table. Subsequently, the hair around the rats' knee joints was removed, and the knee joint area was thoroughly disinfected with 75% ethanol to reduce the risk of infection.

[0048] After disinfection, 200 μL of a 50 g / L papain solution was slowly injected into the knee joint cavity of the rats using a microsyringe. The remaining 12 rats underwent the same procedure, except that an equal volume of physiological saline was injected, serving as a control group.

[0049] Inject once every 2 days. After completing 3 injections, closely observe the morphological and functional changes of the rat knee joint. When the rat knee joint shows obvious swelling, limited movement, and significant abnormalities in flexion and extension function, it indicates that the osteoarthritis model has been successfully established.

[0050] After successful construction, treatment group 1 was injected with 0.5 mg / kg peptide PG155 solution into the knee joint cavity (200g rats were injected with 100 μL of 1 mg / mL peptide solution).

[0051] Treatment group 2 received an injection of 1 mg / kg of polypeptide PG155 solution into the knee joint cavity;

[0052] The control group and the model group received an equal volume of saline injected into the knee joint cavity;

[0053] Each group was given the medication once every 7 days, for a total of 3 injections (i.e., on day 0, day 7, and day 14).

[0054] On day 21, all experimental rats were euthanized, and knee joint cartilage tissue was quickly harvested. The cartilage tissue was then fixed (in 4% paraformaldehyde), dehydrated, embedded (in paraffin), and sectioned. The sections were stained (hematoxylin-eosin and safranin O staining) for subsequent pathological analysis.

[0055] The Mankin's scoring system was used to assess the pathological damage of rat knee joint cartilage tissue. The scoring criteria included four components: tidal line integrity (0-1 points), matrix staining (0-4 points), chondrocytes (0-3 points), and cartilage appearance (0-6 points). The results are shown in Table 1 and... Figure 1 As shown.

[0056] Table 1. The therapeutic effect of peptide PG155 on osteoarthritis-related cartilage damage.

[0057]

[0058] As can be seen from the results in Table 1, the Mankin's score of the OA group was significantly higher than that of the control group, indicating that the osteoarthritis cartilage damage model constructed in this invention has been successfully established.

[0059] Compared to the OA group, the Mankin's scores of both treatment group 1 (injection of 0.5 mg / kg peptide PG155) and treatment group 2 (injection of 1 mg / kg peptide PG155) showed a certain degree of decrease, indicating that peptide PG155 has a certain repairing effect on osteoarthritis-related cartilage damage. However, judging from the specific scores, this treatment effect is relatively limited and failed to significantly reverse the pathological damage state of cartilage tissue.

[0060] Example 2: The therapeutic effect of exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0061] Existing literature indicates that stem cell-derived exosomes can be used to treat osteoarthritis-related cartilage damage. Therefore, this embodiment attempts to combine stem cell exosomes with the peptide PG155 to improve the poor efficacy of PG155 alone.

[0062] (1) Exosome Acquisition

[0063] Bone marrow mesenchymal stem cells (BMSCs) were cultured in DMEM containing 10% fetal bovine serum (exosomes removed by ultracentrifugation) for 24 h.

[0064] Replace with serum-free DMEM medium and continue culturing for 48 hours. Centrifuge and collect the supernatant (a).

[0065] After removing dead cells and large particles by low-speed centrifugation (300g for 10 minutes) and centrifugation (2000g for 20 minutes), the supernatant b was obtained by filtration through a 0.22μm filter membrane to remove impurities.

[0066] After centrifuging supernatant b at 10000g for 30 minutes, collect supernatant c;

[0067] The supernatant c was centrifuged at 100,000g for 70 minutes to precipitate exosomes;

[0068] After resuspending the exosomes in PBS, they were centrifuged again at 100,000g for 70 minutes to obtain the exosomes.

[0069] After resuspending in physiological saline, the exosome concentration was determined by the BCA method and stored at -80℃ for later use.

[0070] Electron microscopy results of exosomes are as follows Figure 3 As shown in a.

[0071] (2) The therapeutic effect of exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0072] The modeling process was the same as in Example 1. Each group contained 12 rats, and the rats in each group were randomly assigned according to the principle of random grouping. The experimental grouping and treatment were as follows:

[0073] The combined group received an intra-articular injection of a mixed solution (100 μL, with a PG155 peptide concentration of 2 mg / mL and an exosome concentration of 1 mg / mL) containing 1 mg / kg of PG155 peptide and 0.5 mg / kg of exosomes.

[0074] The peptide group was injected intra-articularly with 1 mg / kg PG155 peptide solution.

[0075] The exosome group received an intra-articular injection of 0.5 mg / kg exosome solution in the knee joint cavity;

[0076] The control group received an equal volume of physiological saline.

[0077] Each group of animals was given the drug once every 7 days, for a total of 3 injections (i.e., on day 0, day 7, and day 14).

[0078] On day 21, all experimental rats were euthanized, and knee joint cartilage tissue was quickly harvested. The cartilage tissue was then subjected to a series of treatments, including fixation (4% paraformaldehyde), dehydration, embedding (paraffin embedding), sectioning, and staining (hematoxylin-eosin staining and safranin O staining). The pathological damage of the rat knee joint cartilage tissue was assessed using the Mankin's scoring method, and the results are shown in Table 2 and Figure 2.

[0079] Table 2. The therapeutic effect of exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0080]

[0081] As can be seen from the results in Table 2, the Mankin's score of the OA group was significantly higher than that of the control group, indicating that the modeling was successful.

[0082] The Mankin's scores of the peptide group, exosome group, and combination group were all significantly lower than those of the OA group, indicating that all three treatment methods have a certain therapeutic effect on osteoarthritis-related cartilage damage. Moreover, the effect of the combination group was significantly better than that of the peptide group and the exosome group.

[0083] To further test the combined effect, a synergistic analysis of the composition was performed in this embodiment:

[0084] The synergistic effect of the combined use of PG155 peptide and bone marrow mesenchymal stem cell exosomes in the combined treatment group was evaluated using the formula q=E(a+b) / (Ea+Eb-Ea×Eb). In the formula, E(a+b) represents the therapeutic effect of the combined treatment group, Ea represents the therapeutic effect of the peptide group, and Eb represents the therapeutic effect of the exosome group.

[0085] Among them, compared with the OA group, the therapeutic effect of the peptide group was 26.72% (OA group - peptide group / OA group), the therapeutic effect of the exosome group was 31.71%, and the therapeutic effect of the combination group was 55.46%.

[0086] According to Jin Zhengjun's formula, the calculated q value is 1.11, which is slightly lower than the threshold for synergistic effect, indicating that the combined use of peptide PG155 and exosomes has an additive effect rather than a significant synergistic effect in the treatment of osteoarthritis-related cartilage damage.

[0087] Example 3

[0088] Example 2 showed that the combination of ordinary exosomes and peptide PG155 only exhibited an additive effect, with no significant synergistic effect. Therefore, this example attempted to use PG155 to pretreat bone marrow mesenchymal stem cells to generate specially treated exosomes (PG155-Exo), and explored whether its combination with peptide PG155 could produce a significant synergistic therapeutic effect on osteoarthritis-related cartilage damage.

[0089] (1) Acquisition of PG155-Exo exosomes

[0090] Bone marrow mesenchymal stem cells (BMSCs) were cultured for 24 h in DMEM containing 250 µg / mL peptide PG155 and 10% fetal bovine serum (exosomes removed by ultracentrifugation).

[0091] Replace with serum-free DMEM medium and continue culturing for 48 hours. Centrifuge and collect the supernatant (a).

[0092] After removing dead cells and large particles by low-speed centrifugation, impurities were removed by filtration using a 0.22μm filter membrane to obtain supernatant b;

[0093] After centrifuging supernatant b at 10000g for 30 minutes, collect supernatant c;

[0094] The supernatant c was centrifuged at 100,000g for 70 minutes to precipitate exosomes;

[0095] After resuspending the exosomes in PBS, they were centrifuged again at 100,000g for 70 minutes to obtain PG155-Exo exosomes.

[0096] After resuspending in physiological saline, the concentration of PG155-Exo exosomes was determined by BCA method and stored at -80℃ for later use.

[0097] Electron microscopy results of exosomes are as follows Figure 3 As shown in b, compared with untreated bone marrow mesenchymal stem cell exosomes, the exosomes obtained after PG155 treatment were significantly larger in volume, and therefore may contain more contents.

[0098] (2) The therapeutic effect of exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0099] The modeling process was the same as in Example 1. Each group contained 12 rats, and the rats in each group were randomly assigned according to the principle of random grouping. The experimental grouping and treatment were as follows:

[0100] The combined group received intra-articular injections of 1 mg / kg PG155 peptide and 0.5 mg / kg PG155-Exo exosomes in the knee joint.

[0101] The peptide group received an intra-articular injection of 1 mg / kg PG155 peptide in the knee joint.

[0102] The exosome group received an intra-articular injection of 0.5 mg / kg PG155-Exo exosomes in the knee joint cavity;

[0103] The control group and the OA group received an equal volume of saline injected into the knee joint cavity.

[0104] Each group of animals was given the drug once every 7 days, for a total of 3 injections (i.e., on day 0, day 7, and day 14).

[0105] On day 21, all experimental rats were euthanized, and knee joint cartilage tissue was rapidly harvested. The cartilage tissue underwent a series of treatments including fixation (4% paraformaldehyde), dehydration, embedding (paraffin embedding), sectioning, and staining (hematoxylin-eosin staining and safranin O staining). The pathological damage of the rat knee joint cartilage tissue was assessed using the Mankin's scoring method. The results are shown in Table 3. Figure 4 As shown.

[0106] Table 3. Therapeutic effects of PG155-Exo exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0107]

[0108] As shown in Table 3 and Figure 4, the Mankin's score of the combined group was significantly lower than that of the peptide group and the PG155-Exo exosome group. Moreover, compared with the results in Table 2, the Mankin's score of the combined group was significantly lower than that of the ordinary exosome and PG155 combination group.

[0109] Compared to the OA group, the therapeutic efficacy of the peptide group was 25.71%, the therapeutic efficacy of the PG155-Exo exosome group was 44.80%, and the therapeutic efficacy of the combination group was 80.00%.

[0110] The synergistic effect of the combined use of PG155 peptide and PG155-Exo exosomes in the combination group was evaluated using the formula q=E(a+b) / (Ea+Eb-Ea×Eb). In the formula, E(a+b) represents the therapeutic effect of the combination group, Ea represents the therapeutic effect of the peptide group, and Eb represents the therapeutic effect of the PG155-Exo exosome group.

[0111] The calculated q value was 1.36, which is greater than 1.15, indicating that the combination of PG155-Exo exosomes pretreated with peptide PG155 and peptide PG155 can produce a significant synergistic effect in the treatment of osteoarthritis-related cartilage damage.

[0112] To further verify the therapeutic effect of the combined use of peptide PG155 and PG155-Exo exosomes, the cartilage thickness from the cartilage surface to the tideline was calculated using ImageJ analysis software. The results are shown in Table 4. Figure 5 As shown.

[0113] Table 4. Therapeutic effects of PG155-Exo exosomes combined with peptide PG155 on cartilage thickness in osteoarthritis.

[0114]

[0115] As shown in Table 4 and Figure 5, similar to the Mankin's score results, the cartilage thickness in the OA group was significantly decreased, while the cartilage thickness in the polypeptide group, PG155-Exo exosome group and the combined group was significantly increased compared to the OA group.

[0116] Compared to the OA group, the therapeutic efficacy of the peptide group was 25.25%, the therapeutic efficacy of the PG155-Exo exosome group was 42.07%, and the therapeutic efficacy of the combination group was 85.14%.

[0117] The synergistic effect of the combined use of PG155 peptide and PG155-Exo exosomes in the combination group was evaluated using the formula q=E(a+b) / (Ea+Eb-Ea×Eb). In the formula, E(a+b) represents the therapeutic effect of the combination group, Ea represents the therapeutic effect of the peptide group, and Eb represents the therapeutic effect of the PG155-Exo exosome group.

[0118] The q value calculated using the Jin Zhengjun formula is 1.50, which is greater than 1.15. This indicates that the PG155-Exo exosomes generated after pretreatment with peptide PG155, when used in combination with peptide PG155, can synergistically increase cartilage thickness, further verifying the synergistic effect of the two on cartilage damage in osteoarthritis.

[0119] Example 4

[0120] To test whether the combination of peptides PG155 and PG155-Exo exosomes with different mass ratios has the same synergistic effect, this embodiment tested the therapeutic effects of different mass ratio combinations of drugs while keeping the total amount of drugs used constant at 1 mg.

[0121] The modeling process is the same as in Example 1 (6 animals per group, conforming to random grouping), and the grouping is as follows:

[0122] The control group and the OA group received an equal volume of saline injected into the knee joint cavity;

[0123] The peptide group received an intra-articular injection of 1 mg / kg PG155 peptide in the knee joint.

[0124] The exosome group received an intra-articular injection of 1 mg / kg PG155-Exo exosomes into the knee joint cavity;

[0125] Group a received intra-articular injections of 0.5 mg / kg PG155 polypeptide and 0.5 mg / kg PG155-Exo exosomes.

[0126] Group B received intra-articular injections of 0.8 mg / kg PG155 peptide and 0.2 mg / kg PG155-Exo exosomes.

[0127] Group B received intra-articular injections of 0.6 mg / kg PG155 peptide and 0.4 mg / kg PG155-Exo exosomes.

[0128] Each group of animals was given the drug once every 7 days, for a total of 3 injections (i.e., on day 0, day 7, and day 14).

[0129] On day 21, all experimental rats were euthanized, and knee joint cartilage tissue was rapidly harvested. The cartilage tissue underwent a series of treatments, including fixation (4% paraformaldehyde), dehydration, embedding (paraffin embedding), sectioning, and staining (hematoxylin-eosin staining and safranin O staining). The Mankin's scoring method was used to assess the pathological damage of the rat knee joint cartilage tissue. The results are shown in Table 5. Figure 6 and Figure 7 As shown.

[0130] Table 5. Therapeutic effects of PG155-Exo exosomes combined with peptide PG155 on osteoarthritis-related cartilage damage.

[0131]

[0132] From Table 5 and Figure 6 and Figure 7 The results clearly showed that, compared to the "peptide group" using PG155 peptide alone or the "PG155-Exo exosome group" using PG155-Exo exosomes alone, the three combined groups (combination group a, combination group b, and combination group c) showed a significant decrease in Mankin's score and a significant increase in cartilage thickness. This indicates that, with the total drug dosage remaining constant, the combination of PG155 peptide and PG155-Exo exosomes can produce a synergistic effect, thereby more effectively improving osteoarthritis-related cartilage damage.

[0133] Further analysis revealed differences in therapeutic efficacy between combination therapy regimens with varying mass ratios. Specifically, combination group a used a 1:1 mass ratio, combination group b used a 4:1 mass ratio, and combination group c used a 3:2 mass ratio. The results showed that while all three ratios exhibited some synergistic effect, the 1:1 mass ratio of PG155 peptide and PG155-Exo exosomes resulted in the most significant therapeutic effect. This ratio not only minimized the Mankin's score but also maximized the restoration of cartilage thickness, demonstrating optimal cartilage repair capacity.

Claims

1. The use of a polypeptide composition in the preparation of a medicament for the synergistic treatment of cartilage damage in osteoarthritis, characterized in that, The polypeptide composition consists of polypeptide PG155 and PG155-Exo exosomes, wherein polypeptide PG155 is a polypeptide with the N-terminal sequence YTYQKEGLARVLQNN; The mass ratio of the polypeptide PG155 to the PG155-Exo exosome is 2:1; The PG155-Exo exosomes were prepared by the following method: (1) Bone marrow mesenchymal stem cells were cultured for 24 hours in DMEM medium containing 250 µg / mL polypeptide PG155 and fetal bovine serum with exosomes removed by ultracentrifugation; (2) Replace with serum-free DMEM medium and continue culturing for 48 hours, then collect the supernatant; (3) The collected supernatant was subjected to low-speed centrifugation, membrane filtration, high-speed centrifugation and ultracentrifugation in sequence to precipitate and purify the exosomes; (4) After resuspending in PBS, centrifuge again to obtain PG155-Exo exosomes.

2. The use according to claim 1, characterized in that, In the drug, the effective dose of the polypeptide composition is 1.5 mg / kg per dose; The polypeptide composition consists of 1 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes.

3. The use according to claim 2, characterized in that, The solvent for the drug is physiological saline; the drug is delivered by intra-articular injection into the knee joint.

4. A polypeptide composition for synergistic treatment of cartilage damage in osteoarthritis, characterized in that, The polypeptide composition consists of polypeptide PG155 and PG155-Exo exosomes; The polypeptide PG155 is a polypeptide with the N-terminal sequence YTYQKEGLARVLQNN; The PG155-Exo exosomes are exosomes produced by bone marrow mesenchymal stem cells pretreated with the peptide PG155; In the polypeptide composition, the mass ratio of the polypeptide PG155 to the PG155-Exo exosome is 2:1; The PG155-Exo exosomes were prepared by the following method: (1) Bone marrow mesenchymal stem cells were cultured for 24 hours in DMEM medium containing 250 µg / mL polypeptide PG155 and fetal bovine serum with exosomes removed by ultracentrifugation; (2) Replace with serum-free DMEM medium and continue culturing for 48 hours, then collect the supernatant; (3) The collected supernatant was subjected to low-speed centrifugation, membrane filtration, high-speed centrifugation and ultracentrifugation in sequence to precipitate and purify the exosomes; (4) After resuspending in PBS, centrifuge again to obtain PG155-Exo exosomes.

5. The polypeptide composition according to claim 4, characterized in that, The effective dose of the polypeptide composition is 1.5 mg / kg per dose; The polypeptide composition comprises 1 mg / kg polypeptide PG155 and 0.5 mg / kg PG155-Exo exosomes; The polypeptide composition is delivered via intra-articular injection into the knee joint.

Images