Role of transplanted bone marrow cells in development of rotator cuff muscle fatty degeneration in mice

Lawrence V. Klomps, Naseem Zomorodi, Hyun-Min Mike Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Rotator cuff muscle fatty degeneration after a chronic tendon tear is an irreversible pathologic change associated with poor clinical outcomes of tendon repair, and its exact pathogenesis remains unknown. We sought to investigate the role of transplanted bone marrow cells in the development of fatty degeneration, specifically in adipocyte accumulation, using a mouse model. Methods Fourteen mice were divided into 2 bone marrow chimeric animal groups: bone marrow transplantation (BMT) group and reverse BMT group. For the BMT group, C57BL/6J wild-type mice underwent whole body irradiation followed by BMT into the retro-orbital sinus from green fluorescent protein (GFP)-transgenic donor mice. For the reverse BMT group, GFP-transgenic mice received BMT from C57BL/6J wild-type donor mice after irradiation. The supraspinatus tendon, infraspinatus tendon, and suprascapular nerve were surgically transected 3 weeks after transplantation. The rotator cuff muscles were harvested 13 weeks after transplantation for histologic analysis and GFP immunohistochemistry. Results On histologic examination, both groups showed substantial fatty degeneration, fibrosis, and atrophy of the cuff muscles. The BMT group showed no noticeable GFP immunostaining, whereas the reverse BMT group showed significantly stronger GFP staining in most adipocytes (P < .001). However, both groups also showed that a small number of adipocytes originated from transplanted bone marrow cells. A small number of myocytes showed a large cytoplasmic lipid vacuole resembling adipocytes. Conclusions This study's findings suggest that most adipocytes in fatty degeneration of the rotator cuff muscles originate from sources other than bone marrow–derived stem cells, and there may be more than 1 source for the adipocytes.

Original languageEnglish (US)
Pages (from-to)2177-2186
Number of pages10
JournalJournal of Shoulder and Elbow Surgery
Volume26
Issue number12
DOIs
StatePublished - Dec 1 2017

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Rotator Cuff
Bone Marrow Transplantation
Bone Marrow Cells
Adipocytes
Green Fluorescent Proteins
Muscles
Tendons
Transgenic Mice
Transplantation
Muscular Atrophy
Whole-Body Irradiation
Vacuoles
Muscle Cells
Fibrosis
Stem Cells
Bone Marrow
Immunohistochemistry
Staining and Labeling
Lipids
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

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title = "Role of transplanted bone marrow cells in development of rotator cuff muscle fatty degeneration in mice",
abstract = "Background Rotator cuff muscle fatty degeneration after a chronic tendon tear is an irreversible pathologic change associated with poor clinical outcomes of tendon repair, and its exact pathogenesis remains unknown. We sought to investigate the role of transplanted bone marrow cells in the development of fatty degeneration, specifically in adipocyte accumulation, using a mouse model. Methods Fourteen mice were divided into 2 bone marrow chimeric animal groups: bone marrow transplantation (BMT) group and reverse BMT group. For the BMT group, C57BL/6J wild-type mice underwent whole body irradiation followed by BMT into the retro-orbital sinus from green fluorescent protein (GFP)-transgenic donor mice. For the reverse BMT group, GFP-transgenic mice received BMT from C57BL/6J wild-type donor mice after irradiation. The supraspinatus tendon, infraspinatus tendon, and suprascapular nerve were surgically transected 3 weeks after transplantation. The rotator cuff muscles were harvested 13 weeks after transplantation for histologic analysis and GFP immunohistochemistry. Results On histologic examination, both groups showed substantial fatty degeneration, fibrosis, and atrophy of the cuff muscles. The BMT group showed no noticeable GFP immunostaining, whereas the reverse BMT group showed significantly stronger GFP staining in most adipocytes (P < .001). However, both groups also showed that a small number of adipocytes originated from transplanted bone marrow cells. A small number of myocytes showed a large cytoplasmic lipid vacuole resembling adipocytes. Conclusions This study's findings suggest that most adipocytes in fatty degeneration of the rotator cuff muscles originate from sources other than bone marrow–derived stem cells, and there may be more than 1 source for the adipocytes.",
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Role of transplanted bone marrow cells in development of rotator cuff muscle fatty degeneration in mice. / Klomps, Lawrence V.; Zomorodi, Naseem; Kim, Hyun-Min Mike.

In: Journal of Shoulder and Elbow Surgery, Vol. 26, No. 12, 01.12.2017, p. 2177-2186.

Research output: Contribution to journalArticle

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AU - Klomps, Lawrence V.

AU - Zomorodi, Naseem

AU - Kim, Hyun-Min Mike

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N2 - Background Rotator cuff muscle fatty degeneration after a chronic tendon tear is an irreversible pathologic change associated with poor clinical outcomes of tendon repair, and its exact pathogenesis remains unknown. We sought to investigate the role of transplanted bone marrow cells in the development of fatty degeneration, specifically in adipocyte accumulation, using a mouse model. Methods Fourteen mice were divided into 2 bone marrow chimeric animal groups: bone marrow transplantation (BMT) group and reverse BMT group. For the BMT group, C57BL/6J wild-type mice underwent whole body irradiation followed by BMT into the retro-orbital sinus from green fluorescent protein (GFP)-transgenic donor mice. For the reverse BMT group, GFP-transgenic mice received BMT from C57BL/6J wild-type donor mice after irradiation. The supraspinatus tendon, infraspinatus tendon, and suprascapular nerve were surgically transected 3 weeks after transplantation. The rotator cuff muscles were harvested 13 weeks after transplantation for histologic analysis and GFP immunohistochemistry. Results On histologic examination, both groups showed substantial fatty degeneration, fibrosis, and atrophy of the cuff muscles. The BMT group showed no noticeable GFP immunostaining, whereas the reverse BMT group showed significantly stronger GFP staining in most adipocytes (P < .001). However, both groups also showed that a small number of adipocytes originated from transplanted bone marrow cells. A small number of myocytes showed a large cytoplasmic lipid vacuole resembling adipocytes. Conclusions This study's findings suggest that most adipocytes in fatty degeneration of the rotator cuff muscles originate from sources other than bone marrow–derived stem cells, and there may be more than 1 source for the adipocytes.

AB - Background Rotator cuff muscle fatty degeneration after a chronic tendon tear is an irreversible pathologic change associated with poor clinical outcomes of tendon repair, and its exact pathogenesis remains unknown. We sought to investigate the role of transplanted bone marrow cells in the development of fatty degeneration, specifically in adipocyte accumulation, using a mouse model. Methods Fourteen mice were divided into 2 bone marrow chimeric animal groups: bone marrow transplantation (BMT) group and reverse BMT group. For the BMT group, C57BL/6J wild-type mice underwent whole body irradiation followed by BMT into the retro-orbital sinus from green fluorescent protein (GFP)-transgenic donor mice. For the reverse BMT group, GFP-transgenic mice received BMT from C57BL/6J wild-type donor mice after irradiation. The supraspinatus tendon, infraspinatus tendon, and suprascapular nerve were surgically transected 3 weeks after transplantation. The rotator cuff muscles were harvested 13 weeks after transplantation for histologic analysis and GFP immunohistochemistry. Results On histologic examination, both groups showed substantial fatty degeneration, fibrosis, and atrophy of the cuff muscles. The BMT group showed no noticeable GFP immunostaining, whereas the reverse BMT group showed significantly stronger GFP staining in most adipocytes (P < .001). However, both groups also showed that a small number of adipocytes originated from transplanted bone marrow cells. A small number of myocytes showed a large cytoplasmic lipid vacuole resembling adipocytes. Conclusions This study's findings suggest that most adipocytes in fatty degeneration of the rotator cuff muscles originate from sources other than bone marrow–derived stem cells, and there may be more than 1 source for the adipocytes.

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