The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging
Skeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progressio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-10-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.571372/full |
| _version_ | 1818341180048408576 |
|---|---|
| author | Robert V. Musci Maureen A. Walsh Adam R. Konopka Adam R. Konopka Christopher A. Wolff Frederick F. Peelor Raoul F. Reiser Kelly S. Santangelo Karyn L. Hamilton Karyn L. Hamilton |
| author_facet | Robert V. Musci Maureen A. Walsh Adam R. Konopka Adam R. Konopka Christopher A. Wolff Frederick F. Peelor Raoul F. Reiser Kelly S. Santangelo Karyn L. Hamilton Karyn L. Hamilton |
| author_sort | Robert V. Musci |
| collection | DOAJ |
| description | Skeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progression of human musculoskeletal aging is slow, researchers rely on rodent models to identify mechanisms and test interventions. The Dunkin Hartley guinea pig is an outbred strain that begins developing primary osteoarthritis by 4 months of age with a progression and pathology similar to aging humans. The purpose of this study was to determine if skeletal muscle remodeling during the progression of osteoarthritis in these guinea pigs resembles musculoskeletal aging in humans. We compared Dunkin Hartley guinea pigs to Strain 13 guinea pigs, which develop osteoarthritis much later in the lifespan. We measured myofiber type and size, muscle density, and long-term fractional protein synthesis rates of the gastrocnemius and soleus muscles in 5, 9, and 15-month-old guinea pigs. There was an age-related decline in skeletal muscle density, a greater proportion of smaller myofibers, and a decline in type II concomitant with a rise in type I myofibers in the gastrocnemius muscles from Dunkin Hartley guinea pigs only. These changes were accompanied by age-related declines in myofibrillar and mitochondrial protein synthesis in the gastrocnemius and soleus. Collectively, these findings suggest Dunkin Hartley guinea pigs experience myofiber remodeling alongside the progression of osteoarthritis, consistent with human musculoskeletal aging. Thus, Dunkin Hartley guinea pigs may be a model to advance discovery and therapeutic development for human musculoskeletal aging. |
| first_indexed | 2024-12-13T15:54:41Z |
| format | Article |
| id | doaj.art-a0cbd9fb0db94ed29940cf286e6072a0 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-13T15:54:41Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-a0cbd9fb0db94ed29940cf286e6072a02022-12-21T23:39:20ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-10-011110.3389/fphys.2020.571372571372The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal AgingRobert V. Musci0Maureen A. Walsh1Adam R. Konopka2Adam R. Konopka3Christopher A. Wolff4Frederick F. Peelor5Raoul F. Reiser6Kelly S. Santangelo7Karyn L. Hamilton8Karyn L. Hamilton9Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, United StatesDepartment of Health and Exercise Science, Colorado State University, Fort Collins, CO, United StatesDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, United StatesGRECC, William S Middleton Memorial Veterans Hospital, Madison, WI, United StatesDepartment of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL, United StatesAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesDepartment of Health and Exercise Science, Colorado State University, Fort Collins, CO, United StatesDepartment of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Health and Exercise Science, Colorado State University, Fort Collins, CO, United StatesColumbine Health Systems Center for Healthy Aging, Colorado State University, Fort Collins, CO, United StatesSkeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progression of human musculoskeletal aging is slow, researchers rely on rodent models to identify mechanisms and test interventions. The Dunkin Hartley guinea pig is an outbred strain that begins developing primary osteoarthritis by 4 months of age with a progression and pathology similar to aging humans. The purpose of this study was to determine if skeletal muscle remodeling during the progression of osteoarthritis in these guinea pigs resembles musculoskeletal aging in humans. We compared Dunkin Hartley guinea pigs to Strain 13 guinea pigs, which develop osteoarthritis much later in the lifespan. We measured myofiber type and size, muscle density, and long-term fractional protein synthesis rates of the gastrocnemius and soleus muscles in 5, 9, and 15-month-old guinea pigs. There was an age-related decline in skeletal muscle density, a greater proportion of smaller myofibers, and a decline in type II concomitant with a rise in type I myofibers in the gastrocnemius muscles from Dunkin Hartley guinea pigs only. These changes were accompanied by age-related declines in myofibrillar and mitochondrial protein synthesis in the gastrocnemius and soleus. Collectively, these findings suggest Dunkin Hartley guinea pigs experience myofiber remodeling alongside the progression of osteoarthritis, consistent with human musculoskeletal aging. Thus, Dunkin Hartley guinea pigs may be a model to advance discovery and therapeutic development for human musculoskeletal aging.https://www.frontiersin.org/articles/10.3389/fphys.2020.571372/fullagingskeletal muscleprotein synthesismusculoskeletalosteoarthritisanimal model |
| spellingShingle | Robert V. Musci Maureen A. Walsh Adam R. Konopka Adam R. Konopka Christopher A. Wolff Frederick F. Peelor Raoul F. Reiser Kelly S. Santangelo Karyn L. Hamilton Karyn L. Hamilton The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging Frontiers in Physiology aging skeletal muscle protein synthesis musculoskeletal osteoarthritis animal model |
| title | The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging |
| title_full | The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging |
| title_fullStr | The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging |
| title_full_unstemmed | The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging |
| title_short | The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging |
| title_sort | dunkin hartley guinea pig is a model of primary osteoarthritis that also exhibits early onset myofiber remodeling that resembles human musculoskeletal aging |
| topic | aging skeletal muscle protein synthesis musculoskeletal osteoarthritis animal model |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.571372/full |
| work_keys_str_mv | AT robertvmusci thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT maureenawalsh thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT adamrkonopka thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT adamrkonopka thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT christopherawolff thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT frederickfpeelor thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT raoulfreiser thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT kellyssantangelo thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT karynlhamilton thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT karynlhamilton thedunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT robertvmusci dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT maureenawalsh dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT adamrkonopka dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT adamrkonopka dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT christopherawolff dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT frederickfpeelor dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT raoulfreiser dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT kellyssantangelo dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT karynlhamilton dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging AT karynlhamilton dunkinhartleyguineapigisamodelofprimaryosteoarthritisthatalsoexhibitsearlyonsetmyofiberremodelingthatresembleshumanmusculoskeletalaging |