Agaricus bisporus-Derived Glucosamine Hydrochloride Facilitates Skeletal Injury Repair through Bmp Signaling in Zebrafish Osteoporosis Model

Abstract

Glucosamine hydrochloride (GAH), one of the most basic and important derivatives of chitin, is obtained by hydrolysis of chitin in concentrated hydrochloric acid. At present, little is known about how GAH functions in skeletal development. In this report, we demonstrate that GAH, extracted from the cell wall of Agaricus bisporus, acts in a dose-dependent manner to promote not only cartilage and bone development in larvae but also caudal fin regeneration in adult fish. Furthermore, GAH treatment causes a significant increase in expression of bone-related marker genes, indicating its important role in promoting skeletal development. We show that in both larval and adult osteoporosis models induced by high iron osteogenic defects are significantly ameliorated after treatment with GAH, which regulates expression of a series of bone-related genes. Finally, we demonstrate that GAH promotes skeletal development and injury repair through bone morphogenetic protein (Bmp) signaling, and it works at the downstream of the receptor level. Taken together, our findings not only provide a strong research foundation and strategy for the screening of natural osteoporosis drugs and product development using a zebrafish model but also establish the potential for the development of Agaricus bisporus-derived GAH as a new drug for osteoporosis treatment.

Tricrilactones A–H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons fromTrichocladium crispatum, an Alpine Moss‐Associated Fungus

“…However, the transcriptional level of mmp9 was clearly decreased as compared to dexamethasone‐treated zebrafish (Figure 8C). Moreover, we also detected the mRNA levels of bmp2b and bmp4 , two members of bone morphogenetic proteins that induce the formation of bone and cartilage [30, 33] . Results showed that the expression levels of bmp2b and bmp4 were both significantly enhanced in a roughly dose‐dependent manner after treatment of 7 (Figure 8C).…”

“…Moreover, we also detected the mRNA levels of bmp2b and bmp4, two members of bone morphogenetic proteins that induce the formation of bone and cartilage. [30,33] Results showed that the expression levels of bmp2b and bmp4 were both significantly enhanced in a roughly dose-dependent manner after treatment of 7 (Figure 8C). The data showed that tricrilactones may ameliorate osteoporosis by remolding the balance between bone formation and bone resorption, and simultaneously promoting cartilage and skeletal development.…”

“…As osteoporosis is characterized by an imbalance between bone resorption and bone formation, current drugs for osteoporosis either inhibit bone resorption, or stimulate bone formation. [30] Alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) are two biomarkers during osteoporosis, with the former reflecting osteoblast differentiation (bone formation), and the latter embodying the activity of osteoclast (bone resorption). [31] To learn the mechanism for the antiosteoporosis action of tricrilactones on zebrafish, we assessed the quantities of these two markers.…”

“…We initially detected the expression of bonespecific marker genes col2ala and mmp9. The former is a type II collagen synthase related to periosteal ossification and endochondral bone morphogenesis, [30] whereas the latter is a member of the matrix metalloproteinase family that can degrade collagens. [32] Quantitative PCR (qPCR) analysis revealed that administration of 7 dramatically up-regulated col2ala expression, which was comparable to the positive control, alendronate.…”

Tricrilactones A–H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons fromTrichocladium crispatum, an Alpine Moss‐Associated Fungus

“…As osteoporosis is characterized by an imbalance between bone resorption and bone formation, current drugs for osteoporosis either inhibit bone resorption, or stimulate bone formation. [30] Alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) are biomarkers during osteoporosis, with the former reflecting osteoblast differentiation (bone formation), and the latter embodying the activity of osteoclast (bone resorption). [31] To learn the mechanism for the antiosteoporosis action of tricrilactones on zebrafish, we assessed the quantities of these two markers.…”