American Society of Hirudotherapy

Hirudin promotes proliferation and osteogenic differentiation of HBMSCs via activation of cGMP/PKG signaling pathway

Basic science / preclinical published in Bioengineered (2022)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportSalivary PharmacologyDrug DevelopmentCao S et al. · Bioengineered, 2022

Abstract

Osteoporosis is a public health problem resulting in higher susceptibility to bone fracture. Hirudin is known as a direct thrombin inhibitor, which is isolated from the salivary gland of the medicinal leech. The present study aimed to evaluate the effect of Hirudin on the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs). In our study, the effect of Hirudin on the proliferation of HBMSCs was evaluated with the CCK-8 and MTT assays. The capacity of osteogenic differentiation and mineralization of HBMSCs was evaluated with ALP and alizarin red staining, respectively. cGMP content was determined by ELISA. Western blotting and qRT-PCR were used to investigate the effect of Hirudin on the expression of osteoblast-specific markers, including Runx2, osterix (OSX), osteocalcin (OCN), and collagen1 (Col1). In our study, Hirudin treatment promoted cell viability. Moreover, Hirudin treatment increased ALP activity of HBMSCs and red coloration of alizarin. Interestingly, cGMP inhibitor partly reversed the effect of Hirudin on the proliferation, differentiation and mineralization of HBMSCs. In conclusion, Hirudin promoted the proliferation, differentiation and mineralization of HBMSCs via activation of cGMP signaling pathway. Hence, Hirudin contributed to bone remodeling and might represent as an effective agent for the treatment of osteoporosis.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsCell DifferentiationCell ProliferationCells, CulturedCyclic GMP-Dependent Protein KinasesGuanosine MonophosphateHirudinsHumansMicroRNAsOsteogenesisOsteoporosisSignal Transduction

Summary

Cell-line study demonstrating hirudin promotes proliferation, osteogenic differentiation, and mineralization of human bone-marrow mesenchymal stem cells via cGMP/PKG signaling. Potential osteoporosis-treatment indication.

Why This Matters for Hirudotherapy

This study examined whether hirudin — a direct thrombin inhibitor isolated from medicinal leech salivary glands — promotes proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs) in cell culture. The authors found that hirudin increased cell viability, ALP activity, mineralization, and expression of osteoblast markers (Runx2, OSX, OCN, Col1), with a cGMP inhibitor partly reversing these effects, implicating the cGMP signaling pathway. This is directly relevant to ASH's domain, as it explores a leech-derived bioactive molecule's potential therapeutic application beyond anticoagulation — here, bone remodeling and potential osteoporosis treatment. However, the study is limited to cultured human cells; no animal or clinical data are presented, and the findings do not establish clinical efficacy for osteoporosis.

Citation

Hirudin promotes proliferation and osteogenic differentiation of HBMSCs via activation of cGMP/PKG signaling pathway.

Cao S et al. · Bioengineered, 2022

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.