1. INTRODUCTION
Osteoarthritis (OA) is one of the most common debilitating diseases
encountered globally. The clinical symptoms of OA are pain and
functional impairment that includes joint stiffness and dysfunction. It
affects 30 million people in the U.S.(Lawrence et al., 2008). In 80% of
patients with OA have some degree of movement impairment. This leads to
diminished performance in the workplace, and 25% of patients cannot
perform the main activities of their daily life, which often leads to
social isolation and depression(Kean, Kean, & Buchanan, 2004).
Nevertheless, in spite of decades of drug research and development, no
disease-modifying drug for osteoarthritis has been approved for use in
humans(Gerwin, Hops, & Lucke, 2006). Such a drug could slow progression
by reducing the rate of cartilage degeneration. The current standard of
care focuses on pain relief only after symptoms are present, by the use
of acetaminophen, NSAIDs COX2 inhibitors and corticosteroids.
One of the hallmarks of OA is the pathological structural changes that
occur in the subchondral cortical, trabecular bone and subarticular
structures. The early stage in the course of the disease is a
significant increase in bone turnover and re-modelling (both bone
formation and resorption) of the bone cartilage interface, especially in
areas underlying damaged cartilage. The trabecular bone, and the
cortical subchondral plate thickens and becomes increasingly irregular
(Buckland-Wright, 2004). The biomechanical factors, such as localized
increased load on the subarticular bone beneath areas of damaged
cartilage, and pathobiochemical influences, such as enhanced release of
cytokines and tissue growth factors (Haringman, Ludikhuize, & Tak,
2004; Sweeney & Firestein, 2004). Key contributors to catabolic
processes include, interleukin-1β
(IL-1β) and matrix metalloproteinases (MMPs), growth factors and free
radicals, among others(Steinberg & Zeggini, 2016).
Bone morphogenetic proteins (BMPs)
and insulin growth factor 1 (IGF1)
are endogenous anabolic factors that stimulate cartilage generation and
remodelling(Fan et al., 2004; Lajeunesse, 2004; Matsumoto, Gargosky,
Iwasaki, & Rosenfeld, 1996; Sandell & Aigner, 2001). In addition,
health problems of excessive osteoclast formation and bone resorption
can cause an imbalance in bone remodeling and thus induce many adult
skeletal diseases, including osteoporosis, osteoarthritis, rheumatoid
arthritis, multiple myeloma and metastatic cancers, premature menopause
and low levels of testosterone and estrogen in men, all potentially
leading to changes in cartilage homeostasis.
Andrographolide (AG)
is the major active principle
isolated from the plant Andrographis paniculate and
having a similar size or
containing an estrogen-like molecule(Cauley et al., 2008). It is a
well-known traditional medicinal plant in India, Thailand, and China.
This plant is widely recognized for its therapeutic and biologically
active properties. Many studies have focused on andrographolide
(C20H30O5) activity, for
examples, anticancer(Khan, Khan, Farooqui, & Ansari, 2018; Liao et al.,
2019), anti-viral(Paemanee, Hitakarun, Wintachai, Roytrakul, & Smith,
2019; Wintachai et al., 2015), anti-thrombotic(Lu et al., 2012;
Mussbacher et al., 2019), hepatoprotective(Chua, 2014; Singha, Roy, &
Dey, 2007), and anti-inflammatory properties(Tan, Liao, Zhou, & Wong,
2017). Furthermore, AG has been reported to have inhibitory effects on
osteoclastogenesis and osteoclast function in vitro and in
vivo (Zhai et al., 2014). Due to the lack of cytotoxicity and evidence
of the effects of AG on multilineage differentiation in human
mesenchymal stem cells, this study’s aimed is to investigate the effects
of AG on the in-vitro cytotoxicity, and human mesenchymal stem
cell differentiation in order to identify potential mechanisms of
action.
Stimulating bone and cartilage formation with biologically active
pharmaceuticals derived from natural sources is a direction worth
investigating for the treatment of homeostasis of bone diseases and/or
bone remodeling in regenerative medicine field.