## 1 Introduction  
Transcription factors (also known as reprogramming factors) are proteins that can control the transcriptional regulation of genetic information by binding to specific DNA sequences [1; 2]. In 2006 and 2007, ground-breaking research by [PERSON] and [PERSON] demonstrated that forced expression of a set of transcription factors such as c-Myc, Oct3/4, Sox2, and Klf-4, enable reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) that have the ability to self-renew and pluripotency [3; 4]. Over the past decade, numerous studies have been conducted to reprogram and convert somatic cells into targeted phenotypes by using various approaches including genetic manipulation, biomaterials, growth factors, small molecules, and cocktails thereof. The \"direct conversion\" (also known as direct reprogramming) of somatic cells to another differentiated lineage by introducing a combination of transcription factors, is considered to be a more promising strategy, and it involves bypassing the intermediate pluripotent stage [5]. The ability of somatic cells to transdifferentiate into tissue-specificprogeny without going through the time-consuming pluripotent generating step is considered to be a promising strategy for regenerative medicine in clinical settings. These direct conversions include fibroblasts into cardiomyocytes [6; 7], neurons [8; 9; 10; 11], chondrocytes [12; 13; 14] and more in other lineages. However, the process of direct conversion in vitro is still relatively slow and not very efficient, which hinders research on the mechanisms of reprogramming and progress in clinical applications. Approaches that use small molecules for the direct conversion of somatic cells are highly desirable, and it is thought that small molecules can significantly improve their use in therapeutic applications. Using small molecules for reprogramming and conversion of cell lineage is an exciting area of research and this has helped to identify small molecules that promote self-renewal [15; 16; 17; 18; 19], differentiation of stem cells [20; 21; 22; 23; 24], and reprogramming, for example, in the induction of stem cells [25; 26; 27; 28; 29] and direct conversion of somatic cells [30; 31; 32]. It has been shown that small molecules can promote osteogenesis and bone regeneration [21; 33; 34; 35; 36]. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the ability to differentiate into various cell types, such as adipocyte, myoblasts, chondrocytes, and osteoblasts [37; 38]. Among these, osteoblasts play a pivotal role in bone generation, and produce various types of bone extracellular materials, such as type I collagen, osteopontin (OPN), osteoclast (OCN), and bone sialoprotein (BSP) [39]. Osteoblast differentiation is controlled by various transcription factors such as Runt-related transcription factor 2 (Runx2) [40; 41], Osterix [42; 43], and distal-less homeobox 5 (Dlx5) [44; 45]. However, a decline in the number of osteoblasts with respect to osteoclasts can cause an imbalance between bone formation and resorption, and can subsequently lead to pathological conditions such as osteoporosis [46], and bone degeneration-associated tumors such as multiple myeloma [47]. Such regeneration of bone tissue for therapies represents a serious health problem, and remains a significant challenge in terms of clinical feasibility. This is because the available therapeutic approaches are often accompanied by slow treatment, poor efficiency, pain, risk of infection, immunogenicity problems, and tumorigenesis after cell implantation [48]. Therefore, the development of transgene-free therapeutic approaches for bone repair is urgently needed. In this study, we hypothesized that VPA could be used to enhance the differentiation efficiency of MSCs, and it could also improve the efficiency of reprogramming somatic cells to osteoblasts.