PERK activator CCT020312 prevents inflammation-mediated osteoporosis in the ovariectomized rats
| Autor: | Zhuo-Ya Wang, Zhao-Wei Li, Bao-Ming Tang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
endocrine system
medicine.medical_specialty genetic structures Endocrinology Diabetes and Metabolism Ovariectomy Osteoporosis Osteocalcin Enzyme Activators Inflammation Bone and Bones Collagen Type I eIF-2 Kinase Endocrinology Absorptiometry Photon Imaging Three-Dimensional Bone Density Internal medicine Medicine Animals Humans Femur Osteoporosis Postmenopausal business.industry Magnesium silicate Activator (genetics) Tartrate-Resistant Acid Phosphatase Therapeutic effect Obstetrics and Gynecology Organ Size X-Ray Microtomography medicine.disease eye diseases Peptide Fragments Rats Cancellous Bone Ovariectomized rat Osteopontin sense organs medicine.symptom business |
| Zdroj: | Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 37(4) |
| ISSN: | 1473-0766 |
| Popis: | To investigate the therapeutic effects of PERK activator CCT020312 (CCT) on inflammation-mediated osteoporosis (IMO) in ovariectomized rats.Rats were divided into Sham, IMO, IMO + 1 mg/kg CCT and IMO + 2 mg/kg CCT groups. IMO models were constructed by bilateral ovariectomy (OVX) on 1st day followed by injection with magnesium silicate (Talc) on the 59th day. Sham rats did not undergo OVX surgery and were injected with saline instead of Talc. From 60th to 79th day, rats were treated with DMSO (vehicle control) in the Sham and IMO groups, and 1 or 2 mg/kg CCT020312 in treatment groups. Osteopontin (OPN), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type I collagen (CTX-I), and pro-inflammatory factors were measured on the 80th day. ProdigyDEXA was used to evaluate bone mineral density and content (BMD/BMC). Bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N), and trabecular separation (Tb.Sp) was assessed using 3D micro-CT scanner.CCT up-regulated Conn.D, BV/TV, and Tb.N, but down-regulated Tb.Sp in IMO rats. Besides, the declined femoral BMD and BMC in IMO rats were elevated after CCT treatment. Besides, IMO rats represented declined OPN and OCN, as well as increased TRAP, CTX-I, and pro-inflammatory factors, whereas those in the treatment groups were ameliorated regarding these indexes, with 2 mg/kg CCT showing better effect.PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors. |
| Databáze: | OpenAIRE |
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