Regeneration of injured articular cartilage using the recombinant human amelogenin protein
Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The British Editorial Society of Bone & Joint Surgery
2023-10-01
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| Series: | Bone & Joint Research |
| Subjects: | |
| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0019.R1 |
| _version_ | 1797635698816188416 |
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| author | Omer Helwa-Shalom Faris Saba Elad Spitzer Salem Hanhan Koby Goren Shany I. Markowitz Dekel Shilo Nissim Khaimov Yechiel N. Gellman Dan Deutsch Anat Blumenfeld Hani Nevo Amir Haze |
| author_facet | Omer Helwa-Shalom Faris Saba Elad Spitzer Salem Hanhan Koby Goren Shany I. Markowitz Dekel Shilo Nissim Khaimov Yechiel N. Gellman Dan Deutsch Anat Blumenfeld Hani Nevo Amir Haze |
| author_sort | Omer Helwa-Shalom |
| collection | DOAJ |
| description | Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence. Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM+ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion: We found that 0.5 μg/μl rHAM+ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623. |
| first_indexed | 2024-03-11T12:25:04Z |
| format | Article |
| id | doaj.art-c4537746ffe24edd9de060c7b84acc97 |
| institution | Directory Open Access Journal |
| issn | 2046-3758 |
| language | English |
| last_indexed | 2024-03-11T12:25:04Z |
| publishDate | 2023-10-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj.art-c4537746ffe24edd9de060c7b84acc972023-11-06T12:30:11ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582023-10-01121061562310.1302/2046-3758.1210.BJR-2023-0019.R1Regeneration of injured articular cartilage using the recombinant human amelogenin proteinOmer Helwa-Shalom0https://orcid.org/0000-0003-1538-0379Faris Saba1https://orcid.org/0000-0001-8866-5688Elad Spitzer2https://orcid.org/0000-0001-6227-8452Salem Hanhan3https://orcid.org/0000-0001-9217-9738Koby Goren4https://orcid.org/0000-0001-7016-3436Shany I. Markowitz5https://orcid.org/0000-0003-3478-3843Dekel Shilo6https://orcid.org/0000-0001-5926-9723Nissim Khaimov7https://orcid.org/0000-0001-5119-5715Yechiel N. Gellman8https://orcid.org/0000-0003-4913-8812Dan Deutsch9https://orcid.org/0000-0001-5566-5665Anat Blumenfeld10https://orcid.org/0000-0002-1613-050XHani Nevo11https://orcid.org/0000-0002-8311-1341Amir Haze12https://orcid.org/0000-0002-7629-3431The inter-faculty Biotechnology Program, The Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelOrthopedic Surgery Department, Hadassah University Medical Center, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelThe inter-faculty Biotechnology Program, The Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelOrthopedic Surgery Department, Hadassah University Medical Center, Jerusalem, IsraelOrthopedic Surgery Department, Hadassah University Medical Center, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelOrthopedic Surgery Department, Hadassah University Medical Center, Jerusalem, IsraelOrthopedic Surgery Department, Hadassah University Medical Center, Jerusalem, IsraelAims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence. Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM+ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion: We found that 0.5 μg/μl rHAM+ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0019.R1amelogeninarticular cartilageosteochondral injuryarticular cartilagerat modelmesenchymal stem cells (mscs)collagenssubchondral bonecartilageosteochondral injurytype i collagenproteoglycansimmunohistochemistry |
| spellingShingle | Omer Helwa-Shalom Faris Saba Elad Spitzer Salem Hanhan Koby Goren Shany I. Markowitz Dekel Shilo Nissim Khaimov Yechiel N. Gellman Dan Deutsch Anat Blumenfeld Hani Nevo Amir Haze Regeneration of injured articular cartilage using the recombinant human amelogenin protein Bone & Joint Research amelogenin articular cartilage osteochondral injury articular cartilage rat model mesenchymal stem cells (mscs) collagens subchondral bone cartilage osteochondral injury type i collagen proteoglycans immunohistochemistry |
| title | Regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| title_full | Regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| title_fullStr | Regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| title_full_unstemmed | Regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| title_short | Regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| title_sort | regeneration of injured articular cartilage using the recombinant human amelogenin protein |
| topic | amelogenin articular cartilage osteochondral injury articular cartilage rat model mesenchymal stem cells (mscs) collagens subchondral bone cartilage osteochondral injury type i collagen proteoglycans immunohistochemistry |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0019.R1 |
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