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Deficiency of protein phosphatase 5 resists osteoporosis in diabetic mice
Jun Wang1, Changyu Zhao1, Wenpeng Zhao1
1School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China.
Abstract:
Osteoporosis is a common diabetic consequence that negatively affects patients' health and quality of life. Nevertheless, there is mutual interference between clinical drugs intended to regulate blood glucose and bone metabolism. Therefore, it is crucial to look for new treatment targets that effectively control blood glucose and safely protect the bone health of patients with diabetes. In this study, mice given a high-fat diet were shown to be resistant to osteoporosis and diabetes when protein phosphatase 5 (PP5) knockout (KO) mice were used. Serum markers of bone remodeling show that PP5 KO mice are resistant to decreased bone formation and increased bone resorption brought on by diabetes. The absence of PP5 resists the reduction of osteoblast differentiation and the enhancement of osteoclast differentiation in diabetic mice, according to the in vitro osteoblast differentiation of bone mesenchymal stem cells and osteoclast differentiation of bone marrow-derived macrophages. Subsequent investigation revealed that PP5 deficiency increases the expression of the key regulator of osteoblast differentiation, runt-related transcription factor 2, and decreases the activity of the receptor activator of the nuclear factor-κB ligand/osteoprotegerin pathway, a crucial regulatory signaling pathway for osteoclast differentiation. In conclusion, we discovered that PP5 deficiency protects diabetic mice against osteoporosis for the first time.
Insights
Protein phosphatase 5 (PP5) knockout mice resist osteoporosis and diabetes. PP5 deficiency protects bone health by regulating osteoblast and osteoclast differentiation in diabetic conditions.
Area of Science:
- Endocrinology
- Bone Biology
- Metabolic Diseases
Background:
- Diabetes mellitus is a prevalent condition associated with significant morbidity, including an increased risk of osteoporosis.
- Current therapeutic strategies for diabetes often present challenges in managing bone metabolism due to drug interactions.
- Novel therapeutic targets are needed to simultaneously manage hyperglycemia and protect bone health in diabetic patients.
Purpose of the Study:
- To investigate the role of protein phosphatase 5 (PP5) in the development of diabetic osteoporosis.
- To explore PP5 as a potential therapeutic target for managing diabetes-related bone loss.
Main Methods:
- Utilized protein phosphatase 5 (PP5) knockout (KO) mouse models fed a high-fat diet to induce diabetes and obesity.
- Assessed serum markers of bone remodeling, including bone formation and resorption.
- Performed in vitro studies on osteoblast and osteoclast differentiation using bone mesenchymal stem cells and bone marrow-derived macrophages.
Main Results:
- PP5 knockout mice exhibited resistance to both diabetes and osteoporosis.
- Serum analysis revealed that PP5 deficiency prevented diabetes-induced decreases in bone formation and increases in bone resorption.
- In vitro experiments demonstrated that the absence of PP5 inhibited osteoclast differentiation and promoted osteoblast differentiation in diabetic conditions.
- PP5 deficiency was found to upregulate runt-related transcription factor 2 (a key osteoblast regulator) and downregulate the receptor activator of the nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) pathway (critical for osteoclastogenesis).
Conclusions:
- Protein phosphatase 5 (PP5) deficiency confers protection against osteoporosis in a mouse model of diabetes.
- PP5 plays a critical role in regulating bone metabolism during diabetes, making it a potential therapeutic target.
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